Affinage

MUC5B

Mucin-5B · UniProt Q9HC84

Length
5762 aa
Mass
596.3 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUC5B is a large gel-forming polymeric mucin that constitutes the structural backbone of the airway mucus gel and is the predominant secretory mucin of healthy human airways, salivary glands, gallbladder, and endocervix (PMID:30352166, PMID:9147051, PMID:9612268, PMID:9858486). The protein is biosynthesized as a non-O-glycosylated monomer in the ER, dimerizes through C-terminal disulfide linkages (D4-B-C-CK), and is then extensively O-glycosylated before secretion without the major intracellular proteolytic processing seen in von Willebrand factor (PMID:26993521). During its ER maturation the cysteine-rich Cys subdomains are C-mannosylated at WXXW motifs, a modification required for proper folding and ER export (PMID:14718370). Polymer assembly is driven by N-terminal D3-domain disulfide linkages and by calcium-dependent, low-pH head-to-head noncovalent tetramerization of N-terminal dimers via D1-D2 von Willebrand domains, producing compact intragranular assemblies that unfurl into linear mucin bundles upon secretion into bicarbonate-rich, neutral-pH fluid (PMID:24778189, PMID:29440393, PMID:31758042). Functionally, MUC5B is required for mucociliary transport: genetic depletion in human airway cultures impairs mucus mobilization, and biallelic loss-of-function mutation in humans abolishes MUC5B and causes impaired mucociliary clearance, bronchiectasis, and recurrent Staphylococcus aureus infection, establishing MUC5B as an essential innate airway defense component whose congenital deficiency defines a genetic respiratory disease (PMID:36427316, PMID:35023825). Conversely, Muc5b overexpression impairs mucociliary clearance and exacerbates bleomycin-induced lung fibrosis through alveolar ER stress (ATF4/ATF6 activation), reversible by integrated stress response inhibition, linking MUC5B dysregulation to fibroproliferative lung disease (PMID:30560893, PMID:36108173). MUC5B transcription is controlled by a complex array of factors including NF-κB downstream of inflammatory cytokines and cigarette smoke, FOXA2 acting at the IPF-risk rs35705950 enhancer ~3 kb upstream, the ERN2/XBP1S ER-stress pathway in a variant-dependent manner, and SPDEF in healthy but not mucoobstructive airways (PMID:20935193, PMID:28272906, PMID:30973754, PMID:33320836, PMID:29579396).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Establishing that the high-molecular-weight salivary mucin MG1 and the tracheobronchial gene MUC5B are the same product clarified that a single gene generates a major secreted mucin across glandular tissues.

    Evidence cDNA library screening with monoclonal antibody, Northern blot, and in situ hybridization in salivary gland tissue

    PMID:9147051

    Open questions at the time
    • Did not establish polymer assembly or function
    • Glycosylation heterogeneity across tissues not resolved
  2. 1998 High

    Mapping MUC5B to mucous tubules of submucosal glands and to gallbladder and basal colonic goblet cells defined its cellular compartments and tissue distribution distinct from MUC7.

    Evidence In situ hybridization, immunocytochemistry, metabolic labeling, and IHC in human bronchus, gallbladder, and colon

    PMID:9612268 PMID:9651178

    Open questions at the time
    • Functional role in each compartment not tested
    • Regulation of compartment-specific expression unknown
  3. 2000 High

    Dissecting the MUC5B promoter located maximal cell-type-specific transcription within the proximal 223 bp and identified Sp1 and an array of transcription-factor binding sites, providing the first regulatory framework.

    Evidence 5'-deletion luciferase reporters, primer extension, Sp1 co-transfection, and EMSA

    PMID:10840001

    Open questions at the time
    • In vivo relevance of most binding sites untested
    • Distal/enhancer elements not yet examined
  4. 2001 High

    Identifying a highly active distal promoter controlled by ATF-1, PKC, and DNA methylation showed MUC5B expression is governed by both distal cis-elements and epigenetic state.

    Evidence Deletion luciferase reporters, EMSA, methylation analysis, and PMA activation in gastric cancer cells

    PMID:11278696

    Open questions at the time
    • Airway relevance of gastric distal promoter unclear
    • Connection to disease-associated regulation not made
  5. 2004 High

    Demonstrating C-mannosylation of the Cys subdomains at WXXW motifs revealed a co-translational modification required for proper folding and ER export of MUC5B.

    Evidence Recombinant Cys-subdomain expression in COS-7, pulse-chase, WXXW mutagenesis, and C-mannosylation-defective CHO-Lec35.1 cells

    PMID:14718370

    Open questions at the time
    • Effect on full-length polymer assembly not directly shown
    • Enzyme catalyzing C-mannosylation not identified here
  6. 2010 High

    Showing that inflammatory cytokines (IL-1β, IL-17A) and cigarette smoke drive MUC5B via NF-κB binding to a defined upstream site established the inflammatory transcriptional axis controlling MUC5B.

    Evidence Promoter deletion reporters, NF-κB inhibitor, p65 siRNA, ChIP, and EMSA in airway and middle ear epithelial cells

    PMID:18091336 PMID:20935193

    Open questions at the time
    • Relative contribution of each cytokine in vivo unclear
    • Interaction with other regulatory inputs not resolved
  7. 2010 Medium

    Identifying TTF-1 as a repressor and GATA-6 as a lung-specific activator, alongside estrogen-receptor/ERK and neuregulin/ErbB signaling, broadened the network of context-specific MUC5B regulators.

    Evidence Co-transfection and EMSA for TTF-1/GATA; pharmacological inhibition, reporter, and phosphorylation assays for ERα and ErbB pathways in airway epithelial cells

    PMID:18688042 PMID:19556605 PMID:21097527 PMID:21126317

    Open questions at the time
    • Largely single-lab promoter/pharmacology data
    • Endogenous in vivo significance not established
  8. 2016 High

    Resolving the biosynthetic itinerary—ER monomer/dimer, C-terminal disulfide dimerization, O-glycosylated polymer, and secretion without intracellular proteolysis—defined how MUC5B is built and matured.

    Evidence Pulse-chase metabolic labeling, electrophoretic/centrifugal separation, recombinant CT5B biophysics, and neutrophil elastase treatment in primary bronchial epithelial cells

    PMID:26993521

    Open questions at the time
    • Granule packaging dynamics not directly imaged here
    • Glycosylation enzymes not identified
  9. 2018 High

    Structurally defining N-terminal D3-domain disulfide linkage and calcium/low-pH head-to-head tetramerization revealed how MUC5B is compactly packaged in granules and unfurled into linear mucus threads upon secretion.

    Evidence Single-particle EM of recombinant N-terminal constructs, calcium-binding and cross-linking studies, and live microscopy of submucosal gland secretion

    PMID:24778189 PMID:29440393

    Open questions at the time
    • Full-length polymer architecture in vivo not directly resolved
    • Quantitative role of bicarbonate not isolated
  10. 2018 High

    Demonstrating that Muc5b overexpression impairs mucociliary clearance and worsens fibrosis, while SPDEF controls baseline Muc5b only in healthy airways, linked MUC5B level and regulation to mucoobstructive and fibrotic disease.

    Evidence Muc5b transgenic and Spdef/Scnn1b double-mutant mice, bleomycin fibrosis, MCC assays, pharmacological rescue, and human tissue staining

    PMID:29579396 PMID:30560893

    Open questions at the time
    • Spdef-independent driver of Muc5b in disease not identified
    • Mechanism connecting overexpression to fibrosis not yet defined here
  11. 2021 High

    Defining rs35705950 as a functional enhancer where FOXA2 binds, chromatin is accessible, and RNA Pol II loads, mechanistically connected the IPF risk variant to elevated MUC5B transcription and epigenetic remodeling in disease.

    Evidence FOXA2 binding and methylation analysis, nascent transcript analysis, ATAC-seq, and paired single-nucleus RNA-seq/ATAC-seq of IPF lung

    PMID:28272906 PMID:33320836

    Open questions at the time
    • Causal chain from enhancer activity to fibrogenesis incomplete
    • Cell lineages mediating effect not fully delineated
  12. 2022 High

    Genetic loss of MUC5B in human cultures and in a person with biallelic LOF mutation established MUC5B as essential for mucociliary transport and innate airway defense, with deficiency causing bronchiectasis and recurrent infection.

    Evidence CRISPR/shRNA knockdown with live transport imaging in human airway cultures and whole-genome sequencing with deep phenotyping of a family

    PMID:35023825 PMID:36427316

    Open questions at the time
    • Macrophage apoptosis mechanism not fully explained
    • Therapeutic correction not addressed
  13. 2023 High

    Linking Muc5b overexpression to ERN2/XBP1S-driven expression and to ATF4/ATF6 ER stress that ISRIB reverses connected MUC5B dysregulation mechanistically to alveolar stress and fibrogenesis in a variant-dependent manner.

    Evidence Primary HAE cells, ERN2/XBP1 CRISPR and KIRA6 inhibition, transgenic mice, single-cell RNA-seq, ISRIB rescue, and human IPF tissue staining

    PMID:30973754 PMID:36108173

    Open questions at the time
    • Whether ER stress is cause or consequence of fibrosis not fully separated
    • Connection between mucin polymer load and UPR activation incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structural assembly properties of MUC5B mechanistically translate into both protective mucus rheology and pathogenic alveolar accumulation, and what sustains MUC5B expression in mucoobstructive disease independent of SPDEF, remain open.
  • Spdef-independent disease driver of Muc5b unidentified
  • Quantitative link between polymer biophysics and disease phenotype unresolved
  • Glycosylation-modifying enzymes acting on MUC5B not characterized in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-392499 Metabolism of proteins 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
MUC5AC

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The high-molecular-weight salivary mucin MG1 was identified as the product of the tracheobronchial mucin gene MUC5B. In situ hybridization and cDNA library screening showed MUC5B is expressed in all mucous cells of submandibular, sublingual, palatine, and labial salivary glands, while MUC7 is expressed in serous cells. cDNA library screening with monoclonal antibody, Northern analysis, in situ hybridization Glycobiology High 9147051
1998 In human bronchial airways, MUC5B expression is confined exclusively to mucous tubules of submucosal glands, while MUC7 is expressed in a subset of lysozyme-expressing serous tubules, defining distinct cellular compartments within submucosal glands. In situ hybridization and immunocytochemistry on CF and non-CF human bronchus sections American journal of respiratory cell and molecular biology High 9651178
1998 MUC5B is the prominent mucin in human gallbladder (HGBM) and is also expressed and secreted in a subset of colonic goblet cells at the crypt base, but not in the small intestine. Metabolic labeling, Western blotting with anti-MUC5B antibodies, immunohistochemistry, RT-PCR The American journal of physiology High 9612268
1999 The salivary MG1 mucin population is comprised almost entirely of differently glycosylated forms of the MUC5B gene product, as confirmed by amino acid analysis, peptide mapping, Western blot, and antiserum reactivity; the palatal gland is the source of the highly charged MUC5B population. Gel chromatography, isopycnic density gradient centrifugation, anion exchange chromatography, Western blot, monosaccharide/amino acid compositional analysis, peptide mapping Glycobiology High 10024667
1999 MUC5B is the predominant mucin transcript in human endocervix (along with MUC4), and its mRNA expression is inversely correlated with progesterone levels across the menstrual cycle. Semiquantitative RT-PCR with cycle-stage correlation to plasma steroid levels Biology of reproduction Medium 9858486
2000 MUC5B promoter activity is cell-type specific; maximal transcription resides within the first 223 bp upstream of the transcription start site. Sp1 transactivates the MUC5B proximal promoter. The promoter contains binding sites for c-Myc, N-Myc, Sp1, NF-κB, AP-1, CREB, HNF-1, HNF-3, TTF-1, and GRE. Intron 1 contains clustered GA/CACCC boxes binding Sp1, and AP-2alpha and GATA-1 also bind intron 1. 5'-deletion luciferase reporter assays, primer extension for TSS, co-transfection with Sp1, EMSA The Biochemical journal High 10840001
2001 MUC5B protein amount in human cervical mucus peaks at midcycle (coinciding with ovulation), as measured by ELISA using a polyclonal antibody to the D4 domain of MUC5B. ELISA with polyclonal antibody (no. 799) against synthetic D4 peptide, Western blot, immunofluorescence on secretory vesicles The Journal of clinical endocrinology and metabolism Medium 11158014
2001 MUC5B expression in gastric cancer cells is governed by a highly active distal promoter (10× more active than proximal in KATO-III cells) that is upregulated by protein kinase C (PMA treatment). Repression of MUC5B in low-expressing AGS cells is due partly to methylation of the 5'-flanking region. ATF-1 binds a cis-element in the distal promoter; Sp1 specifically transactivates the proximal promoter. RT-PCR, in situ hybridization, transfection with deletion mutants fused to luciferase, binding assays (EMSA), methylation analysis The Journal of biological chemistry High 11278696
2002 The Cys subdomains of MUC5AC and MUC5B are C-mannosylated at their WXXW motifs in the endoplasmic reticulum. Mutation of the first tryptophan in WXXW or expression in C-mannosylation-defective CHO-Lec35.1 cells reduces secretion of the Cys subdomains and causes their retention in the ER, indicating C-mannosylation is required for proper folding and/or ER export. Recombinant Cys subdomain expression in COS-7 cells, pulse-chase with [35S]cysteine/methionine, lectin binding, WXXW mutagenesis, live cell GFP imaging, CHO-Lec35.1 deficient cell line Glycobiology High 14718370
2000 MUC5B mucin gene and its product are expressed in middle ear secretory cells of patients with chronic otitis media, and this expression correlates with infiltration of inflammatory cells in the submucosa, suggesting inflammatory cell products drive MUC5B production. In situ hybridization, immunohistochemistry, AB-PAS staining on 19 patient specimens The Laryngoscope Medium 10764016
2000 MUC5B domains Cys1 and Cys2 selectively bind histatin 1, while Cys8a selectively binds statherin and histatins 1, 3, and 5, as determined by yeast two-hybrid mapping of cysteine-rich subdomains. Yeast two-hybrid system with MUC5B cysteine-rich domain constructs (Cys1–Cys4, Cys8a, Cys8b, Cys8c) Journal of dental research Medium 10728974
2008 17β-estradiol induces MUC5B gene expression in airway epithelial cells via estrogen receptor alpha (ERα) interacting with ERK1/2-MAPK, activating p90RSK1, CREB, and the CRE site at -956 region of the MUC5B promoter. ICI 182,780 (ER antagonist) blocked both ERK1/2 activation and MUC5B expression. RT-PCR, ERK1/2 phosphorylation assays, pharmacological inhibition with ICI 182,780 and ERK inhibitors, MUC5B promoter-CRE reporter assays in human bronchial epithelial cells American journal of respiratory cell and molecular biology Medium 18688042
2008 Cigarette smoke condensate (CSC) activates NF-κB in murine middle ear epithelial cells (mMEEC) and this correlates with Muc5b promoter activation and increased Muc5b mRNA expression, implicating NF-κB as a mediator of smoke-induced Muc5b upregulation. Luciferase reporter assays, EMSA, quantitative transcription factor assays, RT-PCR, qRT-PCR in mMEEC The Laryngoscope Medium 18091336
2009 Neuregulin 1β1 (NRG1β1) induces MUC5B and MUC5AC expression in primary human bronchial epithelial cells via ErbB2 and ErbB3 receptors (but not ErbB4), activating p38 MAPK, ERK1/2, and PI3K pathways; ErbB2 receptor phosphorylation, AKT, and ERK1/2 phosphorylation were demonstrated. Time/dose-response experiments, pharmacological inhibitors of p38 MAPK, ERK1/2, PI3K, Western blot for phosphorylated receptors/kinases, in vivo antigen-challenge mouse model American journal of respiratory cell and molecular biology Medium 19556605
2010 IL-1β and IL-17A induce MUC5B mRNA expression in airway epithelial cells via an NF-κB-based transcriptional mechanism. The regulatory region resides in the -4.17 kb to -2.56 kb region of the MUC5B promoter, and chromatin immunoprecipitation confirmed enhanced binding of the p50 NF-κB subunit to the NF-κB-3 site (-2,921/-2,909) after cytokine stimulation. MUC5B promoter deletion analysis with luciferase reporters, NF-κB inhibitor III treatment, p65 siRNA knockdown, chromatin immunoprecipitation (ChIP) American journal of respiratory cell and molecular biology High 20935193
2010 MCP-1 acting via its receptor CCR2B increases MUC5AC and MUC5B expression in human bronchial epithelial cells through a cascade involving Gq/caveolae, PLCβ, PKC, and (44/42)MAPK. MCP-1 also induces its own expression via RhoA GTPase through CCR2B. Primary NHBE cell cultures, CCR2B shRNA knockdown, pharmacological inhibitors, G-protein studies American journal of physiology. Lung cellular and molecular physiology Medium 21097527
2010 The mouse Muc5b promoter is strongly inhibited by TTF-1 and activated by GATA-4/5/6 transcription factors, as demonstrated by co-transfection and gel-shift assays; GATA-6 binds the Muc5b promoter in a lung-specific context. RT-PCR, co-transfection assays with TTF-1 and GATA factors, gel-shift (EMSA) assays The FEBS journal Medium 21126317
2014 MUC5B assembles as linear disulfide-linked polymers via N-terminal D3-domain-mediated disulfide linkages. Intact polymeric MUC5B has a single high-affinity calcium-binding site distinct from multiple low-affinity sites on each monomer; calcium binding at the D3-domain catalyzes reversible cross-links between MUC5B chains to form networks. At low pH and high calcium, disulfide-linked NT5B dimers (but not monomers) form reversible homotypic head-to-head interactions. Biophysical analysis and single-particle EM of recombinant N-terminal constructs (D1D2D'D3 and subdomains), calcium-binding studies, self-diffusion studies, D3 peptide antibody blocking, cross-linking studies The Journal of biological chemistry High 24778189
2016 MUC5B biosynthesis in primary human bronchial epithelial cells proceeds via: (1) non-O-glycosylated monomer and dimer forms within 20 min of synthesis in the ER; (2) O-glycosylated polymers within 2 h; (3) secretion within 2 h with majority released by 48 h. MUC5B dimerizes by disulfide linkage at the C-terminus (D4-B-C-CK). Unlike von Willebrand factor, MUC5B D-domains undergo no major proteolytic processing intracellularly; degradation occurs extracellularly by neutrophil elastase in CF sputum. Pulse-chase metabolic labeling, electrophoretic and centrifugal separation, biophysical analysis of recombinant CT5B expressed in 293-EBNA cells, neutrophil elastase treatment of MUC5B American journal of physiology. Lung cellular and molecular physiology High 26993521
2017 The MUC5B promoter variant rs35705950 resides within a critical regulatory domain containing a highly conserved FOXA2 binding motif. This region is differentially methylated in association with IPF, MUC5B expression, and rs35705950. FOXA2 binding to this locus is necessary for enhanced MUC5B expression. Identification of FOXA2 binding motif, methylation analysis, FOXA2 binding assays in IPF lung tissue American journal of respiratory cell and molecular biology Medium 28272906
2018 Granule-stored MUC5B N-terminal covalent dimers form head-to-head noncovalent tetramers (via D1-D2 von Willebrand domain interactions) at intragranular pH and high Ca2+, assembling into long linear complexes from which mucin domains project radially. Upon secretion, bicarbonate-rich fluid in submucosal gland ducts unfolds and pulls out MUC5B assemblies into linear threads that form thicker bundles. Single-particle electron microscopy of recombinant MUC5B N-terminal covalent dimer, conventional and video microscopy of mucin secretion in submucosal glands The Journal of biological chemistry High 29440393
2018 Muc5b overexpression in mice causes impaired mucociliary clearance (MCC) in a concentration-dependent manner and worsens bleomycin-induced lung fibrosis. In humans, MUC5B is co-expressed with surfactant protein C (SFTPC) in type 2 alveolar epithelia and in honeycomb cyst epithelial cells. The mucolytic agent P-2119 restores MCC and suppresses bleomycin-induced fibrosis in Muc5b-overexpressing mice. Muc5b-overexpressing transgenic mice, bleomycin lung fibrosis model, mucociliary clearance assays, P-2119 mucolytic treatment, human lung tissue immunostaining for MUC5B/SFTPC co-expression Nature communications High 30560893
2019 The ERN2/XBP1S ER stress pathway regulates MUC5B expression. XBP1S binds the proximal MUC5B promoter and differentially upregulates MUC5B expression in the context of the rs35705950 risk variant. The ERN2-XBP1S pathway forms a positive feedback bistable loop; inhibiting ERN2 with KIRA6 or XBP1 CRISPR-Cas9 reduces MUC5B expression in human airway epithelial cells. Primary human airway epithelial (HAE) cells, transgenic mouse models, XBP1S promoter binding assays, KIRA6 pharmacological inhibition, XBP1 CRISPR-Cas9 knockout, human IPF lung tissue analysis American journal of respiratory and critical care medicine High 30973754
2019 In normal/healthy human airways, MUC5B is the dominant secretory mucin in both the superficial epithelium and submucosal glands throughout the airways (except terminal bronchioles), with distal airways being the predominant expression site. MUC5B and MUC5AC are co-expressed with CCSP-positive secretory cells in proximal superficial epithelium, while MUC5B/CCSP co-positive cells dominate distal regions. Submucosal glands express MUC5B but not MUC5AC. RNA in situ hybridization, immunohistochemistry, droplet digital PCR, air-liquid interface cell cultures from 16 nonsmoker lungs American journal of respiratory and critical care medicine High 30352166
2019 Native MUC5B polymers have a beaded repeating structure along the polymer axis arising from distinct glycosylation patterns. MUC5B adopts a compact conformation in the presence of calcium (10 mM) at pH 5.0; this compaction is lost upon removal of calcium with EGTA or by raising pH to 7.4, suggesting a pathway for intracellular packaging and post-secretory expansion. Electron microscopy of native MUC5B polymers purified from saliva, calcium/pH manipulation experiments, EGTA chelation Scientific reports High 31758042
2021 The rs35705950 variant resides within a classically defined enhancer ~3 kb upstream of MUC5B. Nascent transcript analysis shows RNA polymerase II loads within 10 bp of the G/T transversion site, definitively establishing enhancer function. ATAC-seq shows the region is in accessible chromatin affecting MUC5B expression, and this enhancer is subject to epigenetic remodeling in IPF in both MUC5B-expressing and non-expressing lineages. Nascent transcript analysis (GRO-seq equivalent), ATAC-seq of fresh/cultured human airway epithelial cells, paired single-nucleus RNA-seq and ATAC-seq of IPF lung tissue, nuclease sensitivity assays JCI insight High 33320836
2022 MUC5B is required for mucociliary transport in human airways: MUC5B-deficient human airway epithelial cultures show impaired mucociliary transport, while MUC5AC-deficient cultures show discoordinated (spatially misaligned) transport. These distinct phenotypes demonstrate that MUC5B mobilizes mucus and MUC5AC spatially aligns transport. CRISPR/shRNA-mediated MUC5B or MUC5AC knockdown in human airway epithelial tissue cultures, live mucociliary transport imaging Science advances High 36427316
2022 Congenital biallelic loss-of-function of MUC5B (homozygous splice variant c.1938+1G>A) in humans results in complete absence of MUC5B from saliva, sputum, and nasal samples, impaired mucociliary clearance, bronchiectasis, recurrent Staphylococcus aureus infection, and large numbers of apoptotic macrophages in sputum, defining a new category of genetic respiratory disease. Whole-genome sequencing, immunofluorescence staining, mass spectrometry for mucins, radioaerosol mucociliary clearance measurements, pulmonary function testing, genotyping of family members American journal of respiratory and critical care medicine High 35023825
2022 MUC5B knockout mice show worse lung function, increased inflammatory infiltration, reduced goblet cell differentiation (reduced PAS staining and MUC5AC expression), and increased macrophage secretion of TNF-α and IL-6 with activation of ERK1/2 and NF-κB pathways. MUC5B promotes goblet cell differentiation via STAT6 and SPDEF induction and inhibits inflammation through macrophage function regulation. MUC5B-/- mouse COPD model (24-week cigarette smoke exposure), lung function tests, HE/PAS staining, IHC, Western blot, qPCR, ELISA Respiratory research Medium 35042537
2023 Muc5b overexpression in SFTPC-Muc5b transgenic mice is temporally associated with ER stress markers ATF4 and ATF6 in alveolar epithelia after bleomycin injury. ATF4 and Ddit3 (CHOP) are elevated in alveolar epithelia of SFTPC-Muc5b transgenic mice. Treatment with ISRIB (integrated stress response inhibitor), which facilitates phospho-Eif2α interaction with Eif2B, diminished ATF4 translation and resolved the exaggerated fibrotic response, linking Muc5b-induced ER stress to fibrogenesis. Bulk and single-cell RNA sequencing, transgenic mouse model (SFTPC-Muc5b), bleomycin lung injury model, ISRIB pharmacological treatment, human IPF tissue immunostaining for ATF4/ATF6/MUC5B American journal of respiratory cell and molecular biology High 36108173
2018 SPDEF regulates baseline Muc5b expression in respiratory epithelia (nasopharyngeal and airway, but not olfactory Bowman glands) in mice. In a Muc5b-predominant mucoobstructive disease model (Scnn1b-Tg), Spdef deficiency reduces Muc5ac but not Muc5b expression and does not decrease airway mucus obstruction, indicating Spdef-independent mechanisms sustain Muc5b in mucoobstructive disease. Spdef-deficient mouse characterization, Spdef/Scnn1b-Tg double-mutant mice, BAL mucin content, airway neutrophilia, mucociliary clearance assays American journal of respiratory cell and molecular biology High 29579396

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 A common MUC5B promoter polymorphism and pulmonary fibrosis. The New England journal of medicine 953 21506741
2013 MUC5B promoter polymorphism and interstitial lung abnormalities. The New England journal of medicine 366 23692170
2017 Airway Mucus and Asthma: The Role of MUC5AC and MUC5B. Journal of clinical medicine 282 29186064
2015 TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis. American journal of respiratory and critical care medicine 259 26331942
2019 Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. American journal of respiratory and critical care medicine 233 30352166
2018 Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice. Nature communications 198 30560893
2018 Analysis of protein-altering variants in telomerase genes and their association with MUC5B common variant status in patients with idiopathic pulmonary fibrosis: a candidate gene sequencing study. The Lancet. Respiratory medicine 167 29891356
2004 Quorum sensing-controlled biofilm development in Serratia liquefaciens MG1. Journal of bacteriology 161 14729694
2002 Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung. Respiratory medicine 137 11860173
2013 Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 128 23807779
1998 MUC5B and MUC7 are differentially expressed in mucous and serous cells of submucosal glands in human bronchial airways. American journal of respiratory cell and molecular biology 122 9651178
1999 Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology 118 10024667
2010 NF-κB mediates IL-1β- and IL-17A-induced MUC5B expression in airway epithelial cells. American journal of respiratory cell and molecular biology 115 20935193
2002 The salivary mucin MG1 (MUC5B) carries a repertoire of unique oligosaccharides that is large and diverse. Glycobiology 114 11825880
2007 MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation. American journal of respiratory and critical care medicine 110 17255563
1997 Identification of a major human high molecular weight salivary mucin (MG1) as tracheobronchial mucin MUC5B. Glycobiology 104 9147051
2015 MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. Respirology (Carlton, Vic.) 101 25581455
2001 The Amount of MUC5B mucin in cervical mucus peaks at midcycle. The Journal of clinical endocrinology and metabolism 98 11158014
1999 MUC4 and MUC5B transcripts are the prevalent mucin messenger ribonucleic acids of the human endocervix. Biology of reproduction 96 9858486
2005 Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands. The American journal of surgical pathology 94 15897748
2017 Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 87 28272906
2004 C-Mannosylation of MUC5AC and MUC5B Cys subdomains. Glycobiology 81 14718370
2007 Quorum-sensing regulation of adhesion in Serratia marcescens MG1 is surface dependent. Journal of bacteriology 79 17237163
2000 Sequence of the 5'-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells. The Biochemical journal 77 10840001
2015 MUC5B and Idiopathic Pulmonary Fibrosis. Annals of the American Thoracic Society 76 26595739
2014 Assembly of the respiratory mucin MUC5B: a new model for a gel-forming mucin. The Journal of biological chemistry 72 24778189
2004 Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis. Archives of otolaryngology--head & neck surgery 72 15210557
2016 Combination of Paclitaxel and MG1 oncolytic virus as a successful strategy for breast cancer treatment. Breast cancer research : BCR 69 27503504
2001 Aberrant expression of human mucin gene MUC5B in gastric carcinoma and cancer cells. Identification and regulation of a distal promoter. The Journal of biological chemistry 69 11278696
1998 MUC5B is the prominent mucin in human gallbladder and is also expressed in a subset of colonic goblet cells. The American journal of physiology 69 9612268
1996 Differential expression of human high-molecular-weight salivary mucin (MG1) and low-molecular-weight salivary mucin (MG2). Journal of dental research 69 9003227
2019 XBP1S Regulates MUC5B in a Promoter Variant-Dependent Pathway in Idiopathic Pulmonary Fibrosis Airway Epithelia. American journal of respiratory and critical care medicine 67 30973754
2008 Signal pathway of 17beta-estradiol-induced MUC5B expression in human airway epithelial cells. American journal of respiratory cell and molecular biology 66 18688042
2005 MUC5B glycosylation in human saliva reflects blood group and secretor status. Glycobiology 65 15814823
2000 Immunoquantification of human salivary mucins MG1 and MG2 in stimulated whole saliva: factors influencing mucin levels. Journal of dental research 63 11077992
2019 The MUC5B mucin polymer is dominated by repeating structural motifs and its topology is regulated by calcium and pH. Scientific reports 61 31758042
2015 Effect of Muc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias. Respirology (Carlton, Vic.) 59 26699835
2012 Alternaria sp. MG1, a resveratrol-producing fungus: isolation, identification, and optimal cultivation conditions for resveratrol production. Applied microbiology and biotechnology 58 22526800
2005 Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis. American journal of respiratory and critical care medicine 56 15709052
2014 Maraba MG1 virus enhances natural killer cell function via conventional dendritic cells to reduce postoperative metastatic disease. Molecular therapy : the journal of the American Society of Gene Therapy 55 24695102
2006 Phenotypic diversification and adaptation of Serratia marcescens MG1 biofilm-derived morphotypes. Journal of bacteriology 55 17071749
2018 Development of novel quinoa-based yoghurt fermented with dextran producer Weissella cibaria MG1. International journal of food microbiology 54 29316448
2018 Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma. Cell death & disease 54 29670111
2007 The expression of MUC5AC and MUC5B mucin genes in the mucosa of chronic rhinosinusitis and nasal polyposis. American journal of rhinology 54 17621824
2001 In silico cloning of mouse Muc5b gene and upregulation of its expression in mouse asthma model. American journal of respiratory and critical care medicine 50 11587997
2007 Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome. Annals of the rheumatic diseases 49 17998215
2018 Granule-stored MUC5B mucins are packed by the non-covalent formation of N-terminal head-to-head tetramers. The Journal of biological chemistry 48 29440393
1998 A role for the Pcl9-Pho85 cyclin-cdk complex at the M/G1 boundary in Saccharomyces cerevisiae. Molecular microbiology 46 9593297
2022 MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model. Respiratory research 45 35042537
2022 MUC5B mobilizes and MUC5AC spatially aligns mucociliary transport on human airway epithelium. Science advances 44 36427316
2010 MCP-1/CCR2B-dependent loop upregulates MUC5AC and MUC5B in human airway epithelium. American journal of physiology. Lung cellular and molecular physiology 44 21097527
2019 The Possible Pathogenesis of Idiopathic Pulmonary Fibrosis considering MUC5B. BioMed research international 43 31309122
2012 MUC5B leads to aggressive behavior of breast cancer MCF7 cells. PloS one 42 23056409
2021 Potential clinical utility of MUC5B und TOLLIP single nucleotide polymorphisms (SNPs) in the management of patients with IPF. Orphanet journal of rare diseases 41 33639995
2017 Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma. International journal of cancer 41 28568891
2013 Degradation of MUC7 and MUC5B in human saliva. PloS one 41 23874867
2000 Identification of MUC5B mucin gene in human middle ear with chronic otitis media. The Laryngoscope 38 10764016
2008 Cigarette smoke activates NF kappa B and induces Muc5b expression in mouse middle ear cells. The Laryngoscope 37 18091336
2009 Regulation of neuregulin 1beta1-induced MUC5AC and MUC5B expression in human airway epithelium. American journal of respiratory cell and molecular biology 36 19556605
2019 Modulation of Mucin (MUC2, MUC5AC and MUC5B) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A. Toxins 35 30813459
2014 Modulation of mucin mRNA (MUC5AC and MUC5B) expression and protein production and secretion in Caco-2/HT29-MTX co-cultures following exposure to individual and combined Fusarium mycotoxins. Toxicological sciences : an official journal of the Society of Toxicology 35 24496642
2010 Leptin up-regulates MUC5B expression in human airway epithelial cells via mitogen-activated protein kinase pathway. Experimental lung research 34 20497020
2019 Modulation of intestinal epithelial permeability and mucin mRNA (MUC2, MUC5AC, and MUC5B) expression and protein secretion in Caco-2/HT29-MTX co-cultures exposed to aflatoxin M1, ochratoxin A, and zearalenone individually or collectively. Toxicology letters 33 30904571
2015 Association between MUC5B polymorphism and susceptibility and severity of idiopathic pulmonary fibrosis. International journal of clinical and experimental pathology 33 26823827
2005 Immunohistochemical analysis of MUC5B apomucin expression in breast cancer and non-malignant breast tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 32 16148312
2022 A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality. American journal of respiratory and critical care medicine 31 35771531
2003 Identification and characterization of a GDSL esterase gene located proximal to the swr quorum-sensing system of Serratia liquefaciens MG1. Applied and environmental microbiology 31 12839759
2021 The MUC5B-associated variant rs35705950 resides within an enhancer subject to lineage- and disease-dependent epigenetic remodeling. JCI insight 30 33320836
2018 The relationship between complement C3 expression and the MUC5B genotype in pulmonary fibrosis. American journal of physiology. Lung cellular and molecular physiology 30 29565179
2003 Electron microscopic immunogold localization of salivary mucins MG1 and MG2 in human submandibular and sublingual glands. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 30 12502756
2022 A review on the role of salivary MUC5B in oral health. Journal of oral biosciences 29 36206992
2014 Visfatin induces MUC8 and MUC5B expression via p38 MAPK/ROS/NF-κB in human airway epithelial cells. Journal of biomedical science 29 24885580
2000 Molecular mapping of statherin- and histatin-binding domains in human salivary mucin MG1 (MUC5B) by the yeast two-hybrid system. Journal of dental research 29 10728974
2019 Diesel exhaust particles elevate MUC5AC and MUC5B expression via the TLR4-mediated activation of ERK1/2, p38 MAPK, and NF-κB signaling pathways in human airway epithelial cells. Biochemical and biophysical research communications 27 30857636
2018 Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and Mucoobstructed Mice. American journal of respiratory cell and molecular biology 27 29579396
2021 Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma. Allergology international : official journal of the Japanese Society of Allergology 26 34656442
2017 In vivo imaging of the Muc5b gel-forming mucin. Scientific reports 26 28294161
2017 Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis. Respiratory medicine 25 29206633
2023 Epithelial Endoplasmic Reticulum Stress Enhances the Risk of Muc5b-associated Lung Fibrosis. American journal of respiratory cell and molecular biology 24 36108173
2022 Hereditary Mucin Deficiency Caused by Biallelic Loss of Function of MUC5B. American journal of respiratory and critical care medicine 24 35023825
2021 The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis. Scientific reports 24 34907291
2016 Biosynthesis of the polymeric gel-forming mucin MUC5B. American journal of physiology. Lung cellular and molecular physiology 24 26993521
2011 TRPV1 and TRPA1 stimulation induces MUC5B secretion in the human nasal airway in vivo. Clinical physiology and functional imaging 24 21981454
2010 Improvement of transformation efficiency through in vitro methylation and SacII site mutation of plasmid vector in Bifidobacterium longum MG1. Journal of microbiology and biotechnology 24 20622503
2015 Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients. Auris, nasus, larynx 23 25638393
2023 MG1 interacts with a protease inhibitor and confers resistance to rice root-knot nematode. Nature communications 21 37291108
2022 High Expression of MUC5AC, MUC5B, and Layilin Plays an Essential Role in Prediction in the Development of Plastic Bronchitis Caused by MPP. Frontiers in microbiology 21 35770160
2021 Diverse anti-inflammation and anti-cancer polyketides isolated from the endophytic fungi Alternaria sp. MG1. Fitoterapia 21 34303765
2019 Increase in secreted airway mucins and partial Muc5b STAT6/FoxA2 regulation during Pneumocystis primary infection. Scientific reports 21 30765827
2019 The relationship between MUC5B promoter, TERT polymorphisms and telomere lengths with radiographic extent and survival in a Chinese IPF cohort. Scientific reports 21 31653936
2014 The ocular surface phenotype of Muc5ac and Muc5b null mice. Investigative ophthalmology & visual science 21 24327612
2019 Muc5b is mainly expressed and sialylated in the nasal olfactory epithelium whereas Muc5ac is exclusively expressed and fucosylated in the nasal respiratory epithelium. Histochemistry and cell biology 20 31030254
2013 Substrates and enzyme activities related to biotransformation of resveratrol from phenylalanine by Alternaria sp. MG1. Applied microbiology and biotechnology 20 24068334
2010 The mouse Muc5b mucin gene is transcriptionally regulated by thyroid transcription factor-1 (TTF-1) and GATA-6 transcription factors. The FEBS journal 20 21126317
2024 Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B. American journal of human genetics 19 38991590
2014 MUC5B promoter polymorphisms and risk of coal workers' pneumoconiosis in a Chinese population. Molecular biology reports 19 24924948
2013 Surface-associated MUC5B mucins promote protease activity in Lactobacillus fermentum biofilms. BMC oral health 19 24010726
2012 Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells. Laboratory investigation; a journal of technical methods and pathology 19 22391959
2017 Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments. PloS one 18 28355261
2002 The mouse Muc5b mucin gene: cDNA and genomic structures, chromosomal localization and expression. The Biochemical journal 18 11964160

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