Affinage

LTBP4

Latent-transforming growth factor beta-binding protein 4 · UniProt Q8N2S1

Length
1624 aa
Mass
173.4 kDa
Annotated
2026-06-10
48 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LTBP4 is a secreted extracellular matrix glycoprotein that couples latent TGF-beta sequestration to elastic fiber assembly, functioning as both a structural ECM component and a local regulator of TGF-beta bioavailability (PMID:9660815, PMID:12208849). It is secreted both free and as a disulfide-bonded complex with a TGF-beta LAP-like protein, with TGF-beta binding mediated by its third 8-cysteine (TB) module; an alternatively spliced variant lacking this module fails to bind TGF-beta, allowing cells to tune TGF-beta deposition independent of total expression (PMID:9660815, PMID:11683420). ECM targeting depends on direct binding of the LTBP-4 N-terminal region to fibronectin, and loss of this targeting elevates TGF-beta activity (PMID:18585707). Genetic ablation in mice produces pulmonary emphysema, cardiomyopathy, and colorectal cancer with defective elastic fibers and reduced ECM TGF-beta deposition, where LTBP4 specifically enables TGF-beta1 activation (rather than secretion) and thereby restrains compensatory TGF-beta2/beta3 upregulation and BMP-4 signaling (PMID:12208849, PMID:15466481); recessive loss-of-function mutations cause an analogous human disorder of failed ECM deposition, increased TGF-beta activity, and multi-organ elastic fiber defects (PMID:19836010). LTBP4's structural and TGF-beta-regulatory roles are genetically separable (PMID:19016471). The two isoforms generated from independent promoters are functionally distinct: LTBP-4L complexes with TGF-beta1 and is required for fibulin-4 incorporation into the matrix, whereas LTBP-4S is secreted largely free and is incorporated into the ECM (PMID:20175115, PMID:25713297). Fibulin-4 multimers act as an extracellular chaperone, switching LTBP-4L from a compact to an elongated conformation that enhances fibronectin and fibrillin-1 binding and drives elastogenesis, while fibulin-5 performs the analogous conformational switch on LTBP-4S; N-linked glycans confer isoform-specific control of these axes, which act synergistically (PMID:31548410, PMID:40608550). Beyond the matrix, LTBP4 has context-specific signaling roles, including a cardiomyocyte function in which it is recruited to the MTOC via dynein after angiotensin II stimulation to facilitate NLRP3-NEK7 interaction and inflammasome activation (PMID:42140931).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing LTBP4's basic biochemistry answered whether it physically links TGF-beta to the ECM: it does, via a disulfide-bonded latent complex deposited into matrix and releasable by proteolysis.

    Evidence cDNA cloning, immunoblotting, ECM fractionation, and plasmin treatment of human lung fibroblast secretions

    PMID:9660815

    Open questions at the time
    • Identity of the activating protease(s) in vivo not defined
    • Domain mediating TGF-beta complexing not yet mapped
  2. 1997 Medium

    Domain architecture clarified the structural basis for both functions, predicting microfibrillar/elastic roles and TGF-beta binding capacity.

    Evidence cDNA sequencing and Northern blot defining 20 EGF-like and 4 TB modules and tissue expression

    PMID:9271198

    Open questions at the time
    • No functional reconstitution of predicted activities
    • Which TB module binds TGF-beta not resolved
  3. 2001 Medium

    Mapping TGF-beta binding to the third 8-Cys module showed how alternative splicing can decouple TGF-beta sequestration from total LTBP4 levels.

    Evidence RT-PCR identification of a splice variant and functional TGF-beta binding assay

    PMID:11683420

    Open questions at the time
    • Physiological prevalence and regulation of the splice variant unknown
    • Single lab
  4. 2002 High

    Knockout phenotyping established LTBP4 as both an ECM structural component and a local restraint on TGF-beta signaling, linking its loss to emphysema, cardiomyopathy, and cancer.

    Evidence Gene-trap knockout mouse with histology, phospho-Smad2, and c-myc analyses

    PMID:12208849

    Open questions at the time
    • Whether structural vs signaling defects are separable not addressed here
    • Mechanism of TGF-beta regulation (activation vs deposition) unresolved
  5. 2004 High

    Defining the step LTBP4 controls showed it is required for TGF-beta1 activation, not secretion, with downstream consequences for compensatory TGF-beta isoforms and BMP-4 signaling.

    Evidence Knockout fibroblast microarray, active TGF-beta assay, rescue transfection, and ligand rescue

    PMID:15466481

    Open questions at the time
    • Molecular mechanism by which LTBP4 enables activation not defined
    • LTBP-1 non-redundancy mechanism unclear
  6. 2008 High

    Identifying fibronectin as the ECM-targeting receptor explained how LTBP4 reaches the matrix and how mistargeting elevates TGF-beta activity.

    Evidence Direct binding assays, heparin competition, and FN-null fibroblast analysis

    PMID:18585707

    Open questions at the time
    • Heparin/proteoglycan partner identity in vivo unknown
    • Relationship to fibrillin microfibrils not yet mapped
  7. 2009 High

    Genetic dissection separated LTBP4's two roles, showing elastogenesis and TGF-beta modulation are independent functions; parallel human mutation studies confirmed both functions in human development.

    Evidence Ltbp4S-/- mice with TGF-beta2 knockdown and time-course analysis; patient fibroblast ECM deposition and TGF-beta activity assays

    PMID:19016471 PMID:19836010

    Open questions at the time
    • Molecular basis distinguishing the two functions not resolved
    • Spectrum of human phenotypes incompletely defined
  8. 2010 High

    Resolving isoform behavior showed LTBP-4L and LTBP-4S differ in TGF-beta complexing and ECM targeting, arising from independent promoters.

    Evidence Promoter analysis, conditioned-medium/ECM fractionation, and immunofluorescence

    PMID:20175115

    Open questions at the time
    • Why LTBP-4L is poorly matrix-incorporated alone unexplained at this stage
    • Tissue-specific functional division of labor untested
  9. 2015 High

    Identifying fibulin-4 as a partner of both isoforms, with LTBP-4L required for fibulin-4 matrix incorporation, linked LTBP4 to a specific elastogenic assembly node.

    Evidence Germline knockout comparison, Co-IP/pulldown, and ECM immunofluorescence

    PMID:25713297

    Open questions at the time
    • Mechanism of fibulin-4 incorporation dependence unknown
    • Structural basis of interaction not defined
  10. 2016 High

    In vivo epistasis confirmed LTBP-4L and fibulin-4 act together as a requirement for survival and elastogenesis, and additional work tied LTBP4 to Nrf2/Keap1-PdgfrB regulation downstream of TGF-beta.

    Evidence Ltbp4S-/-;Fibulin-4R/R double mutants; Ltbp4S-/- pathway analysis with TGF-beta dependency

    PMID:27585882 PMID:27645114

    Open questions at the time
    • Nrf2/Keap1 link is single-lab and mechanistically indirect
    • How the LTBP-4L/fibulin-4 partnership executes elastogenesis still molecular-level open
  11. 2017 Medium

    Mechanistic deconstruction of the lung phenotype showed septation defects arise from combined loss of elastic fibers, reduced angiogenesis, and excess TGF-beta-driven fibrosis.

    Evidence Ltbp4-/- lung morphometry, vascular analysis, TGF-beta activity assays

    PMID:28684544

    Open questions at the time
    • Relative contribution of each mechanism not quantified
    • Single lab
  12. 2019 High

    Reconstitution revealed the molecular mechanism of fibulin-4 action: as multimers it chaperones a compact-to-elongated conformational switch in LTBP-4L that enables matrix protein binding and elastogenesis.

    Evidence SEC-MALS, SAXS, Co-IP/pulldown, and cell-free tropoelastin assembly assays

    PMID:31548410

    Open questions at the time
    • In vivo timing of the conformational switch not visualized
    • Whether LTBP-4S uses an analogous mechanism not yet tested
  13. 2025 High

    Completing the dual-axis model, fibulin-5 was shown to drive an analogous conformational extension of LTBP-4S, with N-glycans conferring isoform-specific control of both axes.

    Evidence Glycoproteomics, deglycosylation, biophysical binding, and in vitro elastic fiber assembly assays

    PMID:40608550

    Open questions at the time
    • In vivo synergy of the two axes not genetically tested
    • Glycosyltransferases responsible not identified
  14. 2026 High

    A non-canonical intracellular role was defined: LTBP4 is recruited to the MTOC via dynein and facilitates NLRP3-NEK7 inflammasome assembly in stressed cardiomyocytes.

    Evidence Cardiomyocyte-specific conditional knockout (TAC), Co-IP, MTOC immunofluorescence, and inflammasome activity assays

    PMID:42140931

    Open questions at the time
    • How a secreted ECM protein accesses the cytoplasmic MTOC pool not explained
    • Generality beyond cardiomyocytes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LTBP4's canonical extracellular elastogenic/TGF-beta functions mechanistically relate to its emerging intracellular and tissue-protective signaling roles (Hippo-YAP, renal mitochondrial/angiogenic, inflammasome) remains unresolved.
  • No unifying mechanism connecting extracellular and intracellular pools
  • Many context-specific signaling roles rest on single-lab studies
  • Trafficking that diverts secreted LTBP4 to intracellular compartments undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0140313 molecular sequestering activity 3 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0031012 extracellular matrix 4 GO:0005576 extracellular region 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1474244 Extracellular matrix organization 5 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 2
Partners
ADAMTSL2DYNC1H1FBLN4FBLN5FBN1FN1NLRP3TGFB1
Complex memberships
LTBP4-latent TGF-beta complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 LTBP-4 was identified as a novel member of the LTBP family, cloned from human heart cDNA. It is secreted from cultured human lung fibroblasts both as a free form and in a disulfide-bonded complex with a TGF-beta LAP-like protein, and both forms are deposited into the extracellular matrix. Matrix-associated LTBP-4 is susceptible to proteolytic release by plasmin. cDNA cloning, immunoblotting, ECM fractionation, plasmin treatment assay The Journal of biological chemistry High 9660815
1997 LTBP-4 is a 1587-residue extracellular protein containing 20 EGF-like modules (17 with calcium-binding consensus) and 4 TB (8-cysteine) modules, predicting microfibrillar structure and TGF-beta binding capacity. Highly expressed in heart with presence in skeletal muscle, pancreas, placenta and lung. cDNA sequencing, Northern blot analysis FEBS letters Medium 9271198
2001 A novel alternatively spliced form of LTBP-4 lacking the 3rd 8-Cys repeat (LTBP-4Δ8-Cys3rd) was identified; this splice variant does not bind TGF-beta, providing a mechanism by which cells can decrease TGF-beta deposition without altering total LTBP-4 expression. RT-PCR, functional TGF-beta binding assay, exon-intron structure analysis Journal of cell science Medium 11683420
2002 Disruption of LTBP-4 in mice causes pulmonary emphysema, cardiomyopathy, and colorectal cancer, associated with defective elastic fiber structure and reduced TGF-beta deposition in the ECM. Epithelial cells from knockout mice show reduced phospho-Smad2, overexpressed c-myc, and uncontrolled proliferation, establishing LTBP-4 as both an ECM structural component and a local regulator of TGF-beta signaling. Gene trap knockout mouse model, histology, immunohistochemistry, phospho-Smad2 western blot, c-myc expression analysis Genes & development High 12208849
2004 LTBP-4 deficiency in mouse lung fibroblasts impairs TGF-beta activation (not secretion), leading to compensatory upregulation of TGF-beta2 and -beta3. Loss of LTBP-4-mediated TGF-beta1 activation secondarily enhances BMP-4 signaling by reducing gremlin expression. Transfection of LTBP-4 rescued the knockout fibroblast phenotype; LTBP-1 was ineffective, and treatment with active TGF-beta1 normalized BMP-4 and gremlin expression. Knockout fibroblast analysis, microarray, active TGF-beta assay, rescue transfection, TGF-beta1 treatment The Journal of cell biology High 15466481
2008 LTBP-4 binds directly to fibronectin (FN) through its N-terminal region, and this interaction is indispensable for matrix assembly of LTBP-4. LTBP-4 also has heparin-binding activity in its N-terminal region, and heparin reduces both FN binding and cell adhesion mediated by LTBP-4's C-terminal domain. In FN-null fibroblasts, LTBP-4-mediated ECM targeting is disrupted, resulting in increased TGF-beta activity. Direct binding assays (LTBP-4 to FN), heparin competition assay, FN-null fibroblast analysis, fibroblast adhesion assay, immunofluorescence co-localization Experimental cell research High 18585707
2009 LTBP-4S null mice show defects in elastogenesis visible from E14.5 onward, and air-sac septation defects associated with excessive TGF-beta signaling reversed by lowering TGF-beta2 levels; however, reversal of septation defects was not associated with normalization of elastogenesis, establishing two separate, independent functions of LTBP-4: regulation of elastic fiber assembly and modulation of TGF-beta levels. Ltbp4S-/- mouse model, histology, TGF-beta2 siRNA knockdown, pSmad analysis, time-course analysis E14.5–P7 Journal of cellular physiology High 19016471
2009 Recessive loss-of-function mutations in LTBP4 in humans cause impaired synthesis and failure of LTBP4 deposition into the ECM, resulting in increased TGF-beta activity in cultured fibroblasts and defective elastic fiber assembly across multiple organ systems, establishing LTBP4 as essential for coupling TGF-beta signaling and ECM assembly in human development. Patient fibroblast analysis, LTBP4 ECM deposition assay, TGF-beta activity assay, mRNA stability analysis, Sanger sequencing American journal of human genetics High 19836010
2010 LTBP-4L and LTBP-4S are expressed from two independent promoters with distinct tissue-specific patterns. During secretion, LTBP-4L forms a complex with TGF-beta1 while LTBP-4S is secreted predominantly in free form. LTBP-4S is incorporated into the ECM while full-length LTBP-4L is not readily detectable in the ECM, establishing isoform-specific differences in TGF-beta complexing and ECM targeting. Promoter analysis, RT-PCR, western blot of conditioned medium and ECM fractions, immunofluorescence Journal of cellular physiology High 20175115
2013 The IAAM haplotype of LTBP4 (SNPs V194I, T787A, T820A, T1140M) is associated with prolonged ambulation in DMD patients. Fibroblasts from IAAM individuals show reduced phospho-SMAD signaling in response to TGF-beta compared to VTTT fibroblasts, consistent with LTBP4 as a regulator of TGF-beta bioavailability. SNP haplotype analysis in patient cohort, TGF-beta stimulation assay with phospho-SMAD western blot in patient fibroblasts Annals of neurology Medium 23440719
2015 Both Ltbp-4 isoforms are required for normal elastogenesis and postnatal survival; Ltbp4-/- (null) mice die postnatally with severely defective ECM. Fibulin-4 was identified as a novel interaction partner of both Ltbp-4 isoforms; Ltbp-4L expression is essential for incorporation of fibulin-4 into the ECM. Mouse germline knockout (Ltbp4S-/- vs Ltbp4-/-), co-immunoprecipitation/pulldown for fibulin-4 interaction, immunofluorescence of ECM deposition, comparative histology Disease models & mechanisms High 25713297
2016 LTBP4 induces Pdgfrβ signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGF-beta-dependent manner. In Ltbp4S-/- mice, loss of this pathway contributes to pulmonary emphysema. Ltbp4S-/- mouse model, gene expression analysis, pathway inhibition studies (Nrf2/Keap1), TGF-beta dependency assay Matrix biology Medium 27645114
2016 Ltbp-4L and fibulin-4 functionally interact in vivo; Ltbp4S-/-;Fibulin-4R/R double-mutant mice show dramatically reduced lifespan and severely impaired elastogenesis compared to single mutants, establishing that Ltbp-4L and fibulin-4 act together as a crucial molecular requirement for survival and elastogenesis. Double-mutant mouse genetic epistasis (Ltbp4S-/-;Fibulin-4R/R), survival analysis, histological analysis of lung and aorta Disease models & mechanisms High 27585882
2017 LTBP4 deficiency in Ltbp4-/- mouse lungs contributes to alveolar septation defects through three interacting mechanisms: (1) absence of intact elastic fiber network, (2) reduced angiogenesis, and (3) upregulation of TGF-beta activity resulting in profibrotic processes. Ltbp4-/- mouse lung analysis, vascular morphometry, TGF-beta activity assay, histology, immunohistochemistry American journal of physiology. Lung cellular and molecular physiology Medium 28684544
2018 Pro-inflammatory Ly6C+ macrophages drive fibrosis in DMD via high LTBP4 expression leading to elevated latent-TGF-beta1 production. AMPK activation in macrophages decreases Ltbp4 expression, reduces latent-TGF-beta1, and consequently reduces fibrosis and improves muscle force. Fibro-adipogenic progenitors supply TGF-beta-activating enzymes that act downstream of LTBP4-bound latent TGF-beta1. Mouse macrophage isolation and co-culture, AMPK pharmacological activation, LTBP4 siRNA knockdown, collagen assay, TGF-beta ELISA, muscle force measurement Cell reports High 30463013
2019 Fibulin-4 acts as a molecular extracellular chaperone for LTBP-4L: fibulin-4 multimers (not monomers) induce a conformational switch in LTBP-4L from compact to elongated structure, enhancing LTBP-4L binding to fibronectin and fibrillin-1 and promoting its matrix assembly. This elongated LTBP-4L conformation promotes elastogenesis but only when fibulin-4 is present to escort tropoelastin. Biophysical analysis (SEC-MALS, SAXS), binding assays (Co-IP, pulldown), tropoelastin assembly assay, fibulin-4 monomer vs multimer comparison, cell-free reconstitution Proceedings of the National Academy of Sciences of the United States of America High 31548410
2021 LTBP4 protects against renal tubular interstitial fibrosis (TIF) in a UUO mouse model; Ltbp4S-/- mice show aggravated TIF. Overexpression of LTBP4 in human proximal tubule cells upregulates angiogenic pathways and VEGFA, preserves mitochondrial respiratory function, and the conditioned medium stimulates angiogenesis via upregulated VEGFRs in endothelial cells. UUO mouse model with Ltbp4S-/- mice, LTBP4 overexpression in HK-2 cells, transcriptomics, tube formation assay, mitochondrial respiration assay (Seahorse), VEGFA/VEGFR analysis Cell death & disease Medium 34645813
2021 Aberrant interaction between mutated ADAMTSL2 and LTBP4 variant pairs upregulates TGF-beta signaling in human fibroblasts. The ADAMTSL2-LTBP4 interaction was confirmed, and specific AIS-associated variant pairs disrupt this interaction. Co-immunoprecipitation in human fibroblasts, TGF-beta signaling assay, exome variant analysis Gene Medium 34958866
2022 In melanoma cells, LTBP4 overexpression activates the Hippo signaling pathway (increased YAP1 phosphorylation, MST1 phosphorylation, MOB1 phosphorylation, and nuclear-to-cytoplasmic YAP1 translocation). LTBP4 loss increases the percentage of active TGF-beta1 secreted, and active TGF-beta1 inhibits Hippo-YAP1 signaling. Effects of LTBP4 overexpression on proliferation and metastasis were reversed by YAP1 or MST1 overexpression, establishing a LTBP4-TGF-beta1-Hippo-YAP1 axis. LTBP4 overexpression/knockdown in melanoma cells, Western blot, immunofluorescence, luciferase reporter assay, nude mouse xenograft, FACS Frontiers in cell and developmental biology Medium 35252214
2022 YAP overexpression in vascular smooth muscle cells (VSMCs) upregulates LTBP4 expression. LTBP4 promotes elastic fiber assembly in VSMCs. Silencing LTBP4 in VSMCs abolished the protective role of YAP overexpression against abdominal aortic aneurysm formation in vivo. VSMC-specific YAP overexpression mouse model, LTBP4 siRNA in VSMCs, in vivo AAA model, elastin staining, histology Journal of cardiovascular translational research Medium 35708897
2023 LTBP4 deficiency in mice (Ltbp4 knockdown) increases AKI severity and promotes transition to chronic kidney disease; knockout increases mitochondrial fragmentation (DRP1-dependent), reduces ATP production, decreases mitochondrial respiration and glycolysis. LTBP4-knockdown conditioned media reduces angiogenesis in endothelial cells. DRP1 inhibition with Mdivi-1 ameliorated inflammation and fibrosis in Ltbp4-knockdown mice. Ltbp4-knockdown mouse model (ischemia-reperfusion injury), HK-2 LTBP4 knockdown, Seahorse metabolic assay, tube formation assay, DRP1 inhibitor rescue experiment, electron microscopy of mitochondria Circulation research Medium 37232163
2025 N-linked glycans of LTBP-4L (but not fibulin-4) are critical for fibulin-4-mediated conformational extension of LTBP-4L, impacting its function and assembly. Fibulin-5 strongly interacts with LTBP-4S (not LTBP-4L) and robustly induces conformational extension of LTBP-4S, enhancing fibronectin binding, LTBP-4S ECM deposition, and elastic fiber formation. N-linked glycans of fibulin-5 (but not LTBP-4S) are required for this interaction. Together LTBP-4L/fibulin-4 and LTBP-4S/fibulin-5 axes act synergistically in elastogenesis. Glycoproteomic analysis, enzymatic/recombinant deglycosylation, biophysical binding assays, LTBP-4S/fibulin-5 conformational extension assay, in vitro elastic fiber assembly assay, fibronectin binding assay The FEBS journal High 40608550
2026 In cardiomyocytes, LTBP4 is recruited to the microtubule-organizing center (MTOC) via dynein following angiotensin II stimulation. LTBP4 then facilitates dynein-mediated NLRP3 translocation to the MTOC and promotes NLRP3-NEK7 interaction, thereby driving NLRP3 inflammasome activation. Cardiomyocyte-specific Ltbp4 deficiency attenuates NLRP3 inflammasome activation, cardiac dysfunction, and fibrosis after pressure overload. Pressure overload upregulates LTBP4 partially via the SP1 transcription factor. Cardiomyocyte-specific Ltbp4 conditional knockout mouse (TAC model), Co-IP (LTBP4-dynein, NLRP3-NEK7), immunofluorescence (MTOC localization), SP1 transcription factor analysis, NLRP3 inflammasome activity assays, cardiac function echocardiography Nature communications High 42140931

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Disruption of the gene encoding the latent transforming growth factor-beta binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and colorectal cancer. Genes & development 207 12208849
2013 LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. Annals of neurology 204 23440719
2018 AMPK Activation Regulates LTBP4-Dependent TGF-β1 Secretion by Pro-inflammatory Macrophages and Controls Fibrosis in Duchenne Muscular Dystrophy. Cell reports 181 30463013
2009 Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. American journal of human genetics 124 19836010
1998 Identification and characterization of a new latent transforming growth factor-beta-binding protein, LTBP-4. The Journal of biological chemistry 113 9660815
2014 Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. Journal of neurology, neurosurgery, and psychiatry 78 25476005
1997 Sequence and expression of a novel member (LTBP-4) of the family of latent transforming growth factor-beta binding proteins. FEBS letters 65 9271198
2004 Disruption of LTBP-4 function reduces TGF-beta activation and enhances BMP-4 signaling in the lung. The Journal of cell biology 63 15466481
2009 Dual functions for LTBP in lung development: LTBP-4 independently modulates elastogenesis and TGF-beta activity. Journal of cellular physiology 55 19016471
2008 Fibronectin and heparin binding domains of latent TGF-beta binding protein (LTBP)-4 mediate matrix targeting and cell adhesion. Experimental cell research 55 18585707
2018 Long-range genomic regulators of THBS1 and LTBP4 modify disease severity in duchenne muscular dystrophy. Annals of neurology 43 30014611
2015 Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms. Disease models & mechanisms 40 25713297
2021 The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene. Skeletal muscle 38 34294164
2010 The combined expression pattern of BMP2, LTBP4, and DERL1 discriminates malignant from benign canine mammary tumors. Veterinary pathology 38 20375427
2021 LTBP4 in Health and Disease. Genes 35 34071145
2018 Non-Glycanated Biglycan and LTBP4: Leveraging the extracellular matrix for Duchenne Muscular Dystrophy therapeutics. Matrix biology : journal of the International Society for Matrix Biology 32 29481844
2010 Independent regulation of short and long forms of latent TGF-beta binding protein (LTBP)-4 in cultured fibroblasts and human tissues. Journal of cellular physiology 32 20175115
2019 Fibulin-4 exerts a dual role in LTBP-4L-mediated matrix assembly and function. Proceedings of the National Academy of Sciences of the United States of America 29 31548410
2001 Novel non-TGF-beta-binding splice variant of LTBP-4 in human cells and tissues provides means to decrease TGF-beta deposition. Journal of cell science 24 11683420
2023 LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts. Circulation research 23 37232163
2021 LTBP4 affects renal fibrosis by influencing angiogenesis and altering mitochondrial structure. Cell death & disease 22 34645813
2016 Function of Ltbp-4L and fibulin-4 in survival and elastogenesis in mice. Disease models & mechanisms 22 27585882
2011 Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas. Cellular oncology (Dordrecht, Netherlands) 21 21468687
2017 Role of LTBP4 in alveolarization, angiogenesis, and fibrosis in lungs. American journal of physiology. Lung cellular and molecular physiology 18 28684544
2007 Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 18 17550376
2009 Downregulation of transforming growth factor β (TGFβ) and latent TGFβ binding protein (LTBP)-4 expression in late stage canine mammary tumours. Veterinary journal (London, England : 1997) 16 19836277
2022 Disruption of LTBP4 Inhibition-Induced TGFβ1 Activation Promoted Cell Proliferation and Metastasis in Skin Melanoma by Inhibiting the Activation of the Hippo-YAP1 Signaling Pathway. Frontiers in cell and developmental biology 15 35252214
2019 Clinical and molecular characterization of an 18-month-old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review. Molecular genetics & genomic medicine 11 31115174
2016 Ltbp4 regulates Pdgfrβ expression via TGFβ-dependent modulation of Nrf2 transcription factor function. Matrix biology : journal of the International Society for Matrix Biology 11 27645114
2021 Aberrant interaction between mutated ADAMTSL2 and LTBP4 is associated with adolescent idiopathic scoliosis. Gene 9 34958866
2018 DMD mutation and LTBP4 haplotype do not predict onset of left ventricular dysfunction in Duchenne muscular dystrophy. Cardiology in the young 9 29766838
2022 LTBP4, SPP1, and CD40 Variants: Genetic Modifiers of Duchenne Muscular Dystrophy Analyzed in Serbian Patients. Genes 8 36011296
2020 Disruption of LTBP4 Induced Activated TGFβ1, Immunosuppression Signal and Promoted Pulmonary Metastasis in Hepatocellular Carcinoma. OncoTargets and therapy 8 32764991
2022 Specific Overexpression of YAP in Vascular Smooth Muscle Attenuated Abdominal Aortic Aneurysm Formation by Activating Elastic Fiber Assembly via LTBP4. Journal of cardiovascular translational research 4 35708897
2020 Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature. BMC medical genomics 4 33302946
2022 Autosomal recessive cutis laxa type 1C with a homozygous LTBP4 splicing variant: a case report and update of literature. Molecular biology reports 3 35445908
2022 First report of a short in-frame biallelic deletion removing part of the EGF-like domain calcium-binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C. American journal of medical genetics. Part A 3 35972031
2019 Identification of a Novel 19-bp Deletion Mutation in LTBP4 Using Exome Sequencing in Two Siblings with Autosomal Recessive Cutis Laxa Type 1C. Journal of pediatric genetics 3 32341818
2025 Deleterious variants in LTBP4 are associated with severe pediatric sepsis. Pediatric research 2 41076474
2024 The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy. Journal of neuromuscular diseases 2 38363615
2025 Constitutional epimutations in LTBP4, a component of the TGF-β signaling, and in BRCA1, as potential drivers of early-onset colorectal cancer. Clinical epigenetics 1 41194282
2024 Novel indel variation of LTBP4 gene associates with risk of sudden cardiac death in Chinese populations with coronary artery disease. Legal medicine (Tokyo, Japan) 1 38547642
2024 Epigenetic identification of LTBP4 as a putative tumor suppressor in breast cancer. Epigenomics 1 39193795
2026 LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice. Nature communications 0 42140931
2026 Extracellular matrix remodeling in calcific aortic valve disease: Localized enrichment of type III collagen and LTBP-4. Matrix biology plus 0 42164084
2025 Impact of N-linked glycans on the dual short fibulin/LTBP-4 axes regulating elastogenesis. The FEBS journal 0 40608550
2025 Fibulin-5 promotes fibroblast activation through LTBP-4 to improve the pathogenesis of hemorrhoids. BMC gastroenterology 0 41388516
2022 Association of polymorphisms rs2303729, rs10880, and rs1131620 of LTBP4 with sarcopenia in elderly patients with type 2 diabetes mellitus. Annals of human biology 0 36524797

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