Affinage

ITLN1

Intelectin-1 · UniProt Q8WWA0

Round 2 corrected
Length
313 aa
Mass
35.0 kDa
Annotated
2026-04-28
130 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITLN1 (intelectin-1/omentin) is a secreted, disulfide-linked homotrimeric lectin that functions in innate microbial surveillance and metabolic/vascular signaling. Its crystal structure reveals a Ca²⁺-coordinated binding site that selectively recognizes exocyclic 1,2-diol groups on microbial glycans—including β-D-galactofuranose, phosphoglycerol-modified glycans, heptoses, and KDO—while excluding all tested human glycan epitopes, enabling discrimination of microbial surfaces such as Streptococcus pneumoniae (PMID:26148048, PMID:11313366). As a visceral-fat-derived adipokine, ITLN1 enhances insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes (PMID:16531507), promotes endothelial survival and revascularization through an AMPK→Akt→eNOS/NO cascade (PMID:22081609), suppresses TNF-α-induced vascular inflammation by blocking NADPH oxidase-derived ROS and downstream JNK/p38/COX-2 signaling (PMID:21514279, PMID:22554771), and protects the myocardium from ischemia–reperfusion injury via AMPK- and Akt-dependent anti-apoptotic mechanisms (PMID:24768874). ITLN1 also suppresses colorectal and ovarian tumor progression by inhibiting myeloid-derived suppressor cell accumulation through KEAP1/Nrf2/ROS and NF-κB/PI3K/AKT/GSK3β cascades and by blocking lactotransferrin-induced MMP1 expression (PMID:34363021, PMID:32669559).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2001 High

    Identification of ITLN1 as a Ca²⁺-dependent lectin that selectively recognizes microbial galactofuranose—and simultaneously as a GPI-anchored lactoferrin receptor mediating intestinal iron uptake—established its dual functional identity as both a pattern-recognition molecule and an intestinal receptor.

    Evidence Recombinant protein carbohydrate-binding assays and native gel electrophoresis (lectin function); baculovirus-expressed protein with ¹²⁵I-lactoferrin binding, PI-PLC release, and ⁵⁹Fe uptake in Caco-2 cells (lactoferrin receptor function)

    PMID:11313366 PMID:11747454

    Open questions at the time
    • Structural basis for glycan selectivity was unknown
    • Lactoferrin-receptor function has not been reconciled with lectin activity or confirmed in vivo
    • Native receptor on intestinal epithelium not characterized at the single-cell level
  2. 2005 High

    Discovery that omentin (confirmed identical to intelectin-1) is a visceral-fat-derived adipokine that enhances insulin-stimulated glucose uptake via Akt activation reframed ITLN1 as a metabolic signaling molecule beyond its lectin role.

    Evidence Recombinant omentin treatment of primary human adipocytes with glucose uptake assay and p-Akt Western blot; sequence identity confirmation and tissue expression profiling

    PMID:16386808 PMID:16531507

    Open questions at the time
    • Cell-surface receptor mediating omentin's metabolic effects was not identified
    • Whether insulin-sensitizing activity occurs in vivo in humans was untested
    • Altered expression in Crohn's disease was correlative, not mechanistically dissected
  3. 2008 Medium

    Demonstration that insulin and glucose negatively regulate ITLN1 expression and secretion from omental adipose tissue, including in vivo during hyperinsulinemic clamp, established a feedback loop linking metabolic state to ITLN1 levels.

    Evidence Omental adipose explant culture with insulin/glucose dose-response (RT-PCR, Western blot, ELISA) and hyperinsulinemic-euglycemic clamp in human subjects

    PMID:18174521

    Open questions at the time
    • Transcription factors mediating insulin/glucose suppression were not defined
    • Physiological consequence of reduced ITLN1 in hyperinsulinemic states not established causally
  4. 2011 High

    Pathway dissection in endothelial cells established that ITLN1 activates an AMPK→Akt→eNOS/NO signaling cascade that mediates both anti-inflammatory effects (suppressing TNF-α-induced JNK/COX-2) and pro-angiogenic effects (endothelial survival and revascularization in vivo), with eNOS-knockout mice confirming in vivo eNOS dependence.

    Evidence Recombinant omentin on HUVECs with pharmacological inhibitors and phospho-protein readouts; adenoviral omentin overexpression in mouse limb ischemia model; dominant-negative AMPK/Akt constructs; eNOS-knockout mice

    PMID:21514279 PMID:22081609

    Open questions at the time
    • Upstream receptor for ITLN1 on endothelial cells remains unidentified
    • Whether AMPK activation is direct or requires intermediate kinases was unknown
  5. 2012 High

    Extension to vascular smooth muscle cells showed ITLN1 suppresses TNF-α-induced inflammation by inhibiting NADPH oxidase-derived superoxide, which prevents downstream p38/JNK activation and VCAM-1 expression, broadening its vascular anti-inflammatory mechanism beyond endothelium.

    Evidence Recombinant omentin on SMCs with lucigenin superoxide assay, pharmacological inhibitors (SB203580, SP600125, NAC), monocyte adhesion assay, and ex vivo rat aorta

    PMID:22554771

    Open questions at the time
    • Direct molecular target of ITLN1 on SMCs not identified
    • In vivo relevance to atherosclerosis not tested genetically
  6. 2014 High

    ITLN1 was shown to protect the myocardium from ischemia–reperfusion injury by suppressing cardiomyocyte apoptosis through both AMPK-dependent and Akt-dependent mechanisms, extending its cytoprotective role to cardiac tissue.

    Evidence Mouse I/R model with systemic omentin injection, fat-specific omentin transgenic mice, cardiomyocyte hypoxia/reoxygenation assay, AMPK and Akt inhibitors

    PMID:24768874

    Open questions at the time
    • Whether ITLN1 acts directly on cardiomyocytes or via paracrine intermediates was not resolved
    • No receptor identified on cardiomyocytes
  7. 2015 High

    The 1.6 Å crystal structure resolved how ITLN1 achieves microbial selectivity: a single Ca²⁺ ion coordinates terminal exocyclic 1,2-diol groups present on microbial but not human glycans, explaining why Neu5Ac (sialic acid) is excluded despite containing a 1,2-diol, and glycan microarray confirmed exclusive microbial-epitope binding.

    Evidence X-ray crystallography with β-Galf co-crystal, comprehensive glycan microarray, bacterial cell binding assays with S. pneumoniae serotypes

    PMID:26148048

    Open questions at the time
    • No structure in complex with phosphoglycerol or heptose ligands
    • Downstream signaling triggered upon microbial glycan engagement is unknown
    • Whether ITLN1 opsonizes bacteria for phagocytosis or directly kills them was untested
  8. 2020 Medium

    ITLN1 was shown to suppress ovarian cancer invasion by inhibiting lactotransferrin-induced MMP1 expression and inducing a metabolic shift in metastatic cells, establishing an anti-tumor function in the omental microenvironment.

    Evidence Ovarian cancer invasion/proliferation assays, MMP1 Western blot/qRT-PCR, metabolic profiling, in vivo mouse xenograft model

    PMID:32669559

    Open questions at the time
    • Causal link between lactotransferrin, ITLN1, and MMP1 relies partly on correlation
    • Metabolic shift mechanism not defined at the molecular level
    • Direct binding of ITLN1 to cancer cells vs. stromal-mediated effects not distinguished
  9. 2021 High

    Mechanistic dissection of ITLN1's anti-tumor activity in colorectal cancer revealed suppression of MDSC recruitment through dual inhibition of IL-17D (via KEAP1/Nrf2/ROS) and CXCL2 (via NF-κB), both converging on PI3K/AKT/GSK3β; separately, the CD-associated V109D variant was shown to retain normal glycan binding and oligomerization, and mouse Itln1 knockout increased colitis susceptibility without affecting diet-induced obesity.

    Evidence Orthotopic/subcutaneous xenografts with bone marrow chimera, PI3K inhibitor, MDSC functional assays; recombinant V109D protein binding/oligomerization assays; Itln1 knockout mouse DSS colitis and western-diet models

    PMID:34145348 PMID:34363021 PMID:36072603

    Open questions at the time
    • Whether V109D affects functions beyond glycan binding (e.g. adipokine signaling) is untested
    • Mouse knockout was hypomorphic (~10,000-fold reduction), not a true null
    • Receptor mediating ITLN1's PI3K/AKT activation on tumor cells is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the cell-surface receptor through which ITLN1 activates AMPK/Akt signaling on endothelial cells, cardiomyocytes, adipocytes, and tumor cells remains entirely unknown, representing the central unresolved question in ITLN1 biology.
  • No receptor has been identified for ITLN1 adipokine/signaling functions
  • Whether lectin (glycan-binding) and adipokine (signaling) functions use the same or distinct receptors is unknown
  • Effector mechanisms downstream of microbial glycan recognition (opsonization, complement, direct killing) are uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0048018 receptor ligand activity 4 GO:0008289 lipid binding 2 GO:0038024 cargo receptor activity 1
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-1643685 Disease 2
Partners
AKT1LTFMMP1NFE2L2NFKB1NOS3PRKAA1

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Human intelectin-1 (hIntL-1/ITLN1) was identified as a secretory glycoprotein that exists as a ~120 kDa homotrimer (three ~40 kDa subunits bridged by disulfide bonds) and binds D-galactofuranosyl residues and D-pentoses in a Ca2+-dependent manner, specifically recognizing bacterial arabinogalactan of Nocardia containing D-galactofuranosyl residues but not mammalian glycans. Recombinant protein expression, carbohydrate binding assays, native gel electrophoresis, Western blot under reducing/non-reducing conditions, RT-PCR for tissue expression The Journal of biological chemistry High 11313366
2001 ITLN1 was cloned as a human intestinal lactoferrin receptor (LfR); the recombinant protein bound human lactoferrin with an apparent Kd of ~360 nM in a partially Ca2+-dependent manner, appeared as 136 kDa under non-reducing and 34 kDa under reducing conditions (consistent with a disulfide-linked homotetramer/multimer), was GPI-anchored on Caco-2 cells, and its overexpression in Caco-2 cells increased 125I-lactoferrin binding (1.7-fold) and 59Fe-lactoferrin uptake (3.4-fold), implicating it in iron uptake from lactoferrin. cDNA cloning, baculovirus expression/purification, 125I-lactoferrin binding assays, PI-PLC treatment, transfection into Caco-2 cells, 59Fe uptake assay Biochemistry High 11747454
2005 Omentin (ITLN1) was identified as a novel visceral fat depot-specific secretory adipokine; recombinant omentin enhanced insulin-stimulated glucose uptake in human subcutaneous (~47%) and omental (~30%) adipocytes in vitro, and increased Akt phosphorylation both in the absence and presence of insulin, indicating it sensitizes adipocytes to insulin signaling through Akt activation. Recombinant protein treatment of primary human adipocytes, glucose uptake assay, Western blot for p-Akt, EST library sequencing, Northern blot for tissue distribution American journal of physiology. Endocrinology and metabolism High 16531507
2005 ITLN1/omentin gene structure was characterized, its promoter region defined, and sequence comparison revealed 100% identity between omentin and human intelectin-1, establishing these as the same protein. Omentin mRNA expression was found to differ in omental adipose tissue from patients with Crohn's disease, suggesting a role in intestinal barrier defense. Genomic sequencing, sequence alignment, RT-PCR of adipose tissue from IBD patients Biochimica et biophysica acta Medium 16386808
2011 Omentin (ITLN1) inhibits TNF-α-induced vascular inflammation in human endothelial cells by activating AMPK (phospho-Thr172) and eNOS (phospho-Ser1177), increasing cGMP levels, and suppressing TNF-α-induced JNK phosphorylation and COX-2 expression; NOS inhibition reversed omentin's anti-inflammatory effect, placing eNOS/NO downstream of AMPK in the omentin signaling pathway. Recombinant omentin treatment of HUVECs, Western blot for phospho-AMPK/eNOS/JNK, enzyme immunoassay for cGMP, pharmacological inhibitors (NOS inhibitor, JNK inhibitor) Biochemical and biophysical research communications High 21514279
2011 Omentin (ITLN1) promotes endothelial cell survival, differentiation into vascular tube-like structures, and ischemia-induced revascularization in vivo through an Akt→eNOS signaling pathway; AMPK acts upstream of Akt in this cascade, as dominant-negative AMPK reduced omentin-induced Akt phosphorylation; eNOS-knockout mice showed no revascularization response to omentin, confirming eNOS dependence in vivo. Adenoviral omentin overexpression in mice (limb ischemia model), HUVEC differentiation/survival assays with recombinant omentin, dominant-negative Akt/AMPK constructs, PI3K inhibitor (LY294002), NOS inhibitor, eNOS-knockout mice, Western blot for p-Akt/p-eNOS/p-AMPK The Journal of biological chemistry High 22081609
2012 Omentin (ITLN1) exerts anti-inflammatory effects in vascular smooth muscle cells by inhibiting TNF-α-induced superoxide production (NADPH oxidase activity), thereby preventing downstream activation of p38 and JNK kinases and suppression of VCAM-1 expression and monocyte adhesion; antioxidant N-acetyl-L-cysteine mimicked omentin's effect, confirming the ROS-dependent mechanism. Recombinant omentin treatment of SMCs, Western blot for p-p38/p-JNK/VCAM-1, lucigenin assay for NADPH oxidase activity, p38 and JNK inhibitors (SB203580, SP600125), N-acetyl-L-cysteine, monocyte adhesion assay, ex vivo rat aorta European journal of pharmacology High 22554771
2014 Omentin (ITLN1) protects the myocardium from ischemia/reperfusion injury by suppressing cardiomyocyte apoptosis through both AMPK-dependent and Akt-dependent mechanisms; systemic omentin administration reduced infarct size in mice, and both fat-specific omentin overexpression and recombinant omentin in cultured cardiomyocytes (hypoxia/reoxygenation model) showed reduced apoptosis that was reversed by AMPK or Akt blockade. Mouse I/R model with systemic omentin injection, fat-specific omentin transgenic mice, cultured cardiomyocyte hypoxia/reoxygenation assay, AMPK and Akt inhibitors, Western blot for p-AMPK/p-Akt, apoptosis assays Journal of the American College of Cardiology High 24768874
2015 Crystal structure of hIntL-1 (ITLN1) at 1.6 Å resolution complexed with β-D-galactofuranose (β-Galf) revealed that ITLN1 uses a bound calcium ion to coordinate terminal exocyclic 1,2-diol groups of microbial glycans; glycan microarray profiling showed ITLN1 binds exclusively microbial glycan epitopes (β-Galf, D-phosphoglycerol-modified glycans, heptoses, KO, KDO) and not any known human glycan epitopes; Neu5Ac (sialic acid), which also contains an exocyclic 1,2-diol, does not bind due to steric/electronic incompatibility; ITLN1 selectively marks Streptococcus pneumoniae serotypes bearing surface 1,2-diol glycans. X-ray crystallography (1.6 Å resolution), glycan microarray screening, recombinant protein, bacterial cell binding assays Nature structural & molecular biology High 26148048
2020 ITLN1 suppresses ovarian cancer cell invasion and proliferation in the omental tumor microenvironment by: (1) inhibiting lactotransferrin-induced MMP1 expression to reduce invasive potential, and (2) inducing a metabolic shift in metastatic ovarian cancer cells; in vivo, ITLN1-treated tumor-bearing mice showed marked decreases in tumor growth rates. Ovarian cancer cell invasion/proliferation assays, MMP1 expression (Western blot/qRT-PCR), metabolic profiling, in vivo mouse xenograft model with ITLN1 treatment Nature communications Medium 32669559
2021 ITLN1 suppresses colorectal carcinoma progression by inhibiting tumor vascularization and myeloid-derived suppressor cell (MDSC) accumulation; mechanistically, ITLN1 suppressed tumor-derived IL-17D via the KEAP1/Nrf2/ROS/IL-17D cascade and CXCL2 via p65 NF-κB/CXCL2 signaling, both dependent on PI3K/AKT/GSK3β; PI3K inhibitor LY294002 reversed these effects; ITLN1 also directly inhibited bone marrow HPC differentiation into MDSCs and NOS2 activity on MDSCs. Orthotopic and subcutaneous tumor xenografts, bone marrow transplantation (H-2b+YFP+ chimerism), ITLN1 overexpression in CRC cells, PI3K inhibitor, Western blot for KEAP1/Nrf2/NF-κB/AKT/GSK3β pathway components, MDSC functional assays (T cell suppression, NOS2, ROS), ELISA for IL-17D/CXCL2 Oncogene High 34363021
2021 The ITLN1 missense variant V109D does not alter glycan binding to β-D-galactofuranose or protein oligomerization, indicating this CD-risk-associated variant is functionally neutral for these core molecular activities; ITLN1 protein in the intestine is goblet-cell derived in humans. Glycan binding assays with recombinant V109D variant protein, oligomerization assays (native PAGE/SEC), immunohistochemistry/immunofluorescence of intestinal tissue Scientific reports Medium 34145348
2022 In C57BL/6 mice, the functional ortholog Itln1 is expressed in Paneth cells (not goblet cells as in humans) of the small intestine; Itln1 knockout mice (hypomorphic allele, ~10,000-fold reduction) showed increased susceptibility to acute DSS-induced colitis but no significant effect on diet-induced obesity in two western-diet models, suggesting Itln1 plays a role in intestinal innate immunity but is not a major determinant of obesity/metabolic phenotype in this model. Itln1 knockout mouse generation (hypomorphic trapping allele), DSS colitis model (acute and chronic), diet-induced obesity model, Western blot and qRT-PCR for tissue expression, IHC for cell-type localization Frontiers in immunology Medium 36072603
2008 Insulin and glucose dose-dependently decreased omentin-1 (ITLN1) mRNA expression, protein levels, and secretion from omental adipose tissue explants ex vivo; hyperinsulinemic clamp in healthy subjects reduced plasma omentin-1 levels in vivo, establishing negative regulation of ITLN1 by insulin and glucose. Omental adipose tissue explant culture with insulin/glucose treatment, RT-PCR, Western blot, ELISA, hyperinsulinemic-euglycemic clamp in human subjects Diabetes Medium 18174521

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
2008 Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nature genetics 2108 18587394
2010 Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nature genetics 2036 21102463
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1998 HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proceedings of the National Academy of Sciences of the United States of America 1305 9501201
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2006 Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. American journal of physiology. Endocrinology and metabolism 672 16531507
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2007 Omentin plasma levels and gene expression are decreased in obesity. Diabetes 576 17329619
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2004 Cardiac physiology at the cellular level: use of cultured HL-1 cardiomyocytes for studies of cardiac muscle cell structure and function. American journal of physiology. Heart and circulatory physiology 338 14766671
2005 Mammalian lactoferrin receptors: structure and function. Cellular and molecular life sciences : CMLS 296 16261254
2001 Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall. The Journal of biological chemistry 295 11313366
2005 Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochimica et biophysica acta 291 16386808
2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome research 285 12975309
2001 Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry 269 11747454
2011 Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochemical and biophysical research communications 248 21514279
2010 Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes research and clinical practice 239 20129687
2008 Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 223 18174521
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2010 Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes 196 20682687
2014 H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation. Biochimica et biophysica acta 195 25450968
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2014 Omentin prevents myocardial ischemic injury through AMP-activated protein kinase- and Akt-dependent mechanisms. Journal of the American College of Cardiology 142 24768874
2011 Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism. The Journal of biological chemistry 140 22081609
2015 Recognition of microbial glycans by human intelectin-1. Nature structural & molecular biology 132 26148048
2012 Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells. European journal of pharmacology 130 22554771
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2017 Doxorubicin-induced oxidative stress: The protective effect of nicorandil on HL-1 cardiomyocytes. PloS one 108 28245258
1999 Hypoxia regulates the expression of the adrenomedullin and HIF-1 genes in cultured HL-1 cardiomyocytes. Biochemical and biophysical research communications 95 10558876
2002 Functional expression of the hyperpolarization-activated, non-selective cation current I(f) in immortalized HL-1 cardiomyocytes. The Journal of physiology 77 12433951
2011 Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. American journal of physiology. Heart and circulatory physiology 74 21278133
2004 Calpain inhibition prevents pacing-induced cellular remodeling in a HL-1 myocyte model for atrial fibrillation. Cardiovascular research 69 15158144
2011 PKC-dependent coupling of calcium permeation through transient receptor potential canonical 3 (TRPC3) to calcineurin signaling in HL-1 myocytes. Proceedings of the National Academy of Sciences of the United States of America 67 21653882
2011 Mitochondria-cytoskeleton interaction: distribution of β-tubulins in cardiomyocytes and HL-1 cells. Biochimica et biophysica acta 65 21296049
2016 miR-208b upregulation interferes with calcium handling in HL-1 atrial myocytes: Implications in human chronic atrial fibrillation. Journal of molecular and cellular cardiology 59 27545043
2004 Hypoxia regulates the adenosine transporter, mENT1, in the murine cardiomyocyte cell line, HL-1. Cardiovascular research 59 14985075
2013 The mitochondrial Na+-Ca2+ exchanger, NCLX, regulates automaticity of HL-1 cardiomyocytes. Scientific reports 52 24067497
2001 Endothelin-1 induces phosphorylation of GATA-4 transcription factor in the HL-1 atrial-muscle cell line. The Biochemical journal 51 11583584
2020 ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment. Nature communications 50 32669559
2015 Molecular Mechanisms Underlying Urate-Induced Enhancement of Kv1.5 Channel Expression in HL-1 Atrial Myocytes. Circulation journal : official journal of the Japanese Circulation Society 49 26477273
2012 NOX4-Dependent Hydrogen Peroxide Overproduction in Human Atrial Fibrillation and HL-1 Atrial Cells: Relationship to Hypertension. Frontiers in physiology 46 22679437
2008 Distinct organization of energy metabolism in HL-1 cardiac cell line and cardiomyocytes. Biochimica et biophysica acta 46 18423391
2011 Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium. Biochemical and biophysical research communications 45 22079292
2004 Functional expression of L- and T-type Ca2+ channels in murine HL-1 cells. Journal of molecular and cellular cardiology 44 14734053
2013 Regulation of autophagy and apoptosis in response to angiotensin II in HL-1 cardiomyocytes. Biochemical and biophysical research communications 41 24099770
2016 ZFHX3 knockdown increases arrhythmogenesis and dysregulates calcium homeostasis in HL-1 atrial myocytes. International journal of cardiology 39 26930642
2015 cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes. American journal of physiology. Cell physiology 38 26224577
2014 Iron overload and apoptosis of HL-1 cardiomyocytes: effects of calcium channel blockade. PloS one 38 25390893
2012 Reduction of STAT3 expression induces mitochondrial dysfunction and autophagy in cardiac HL-1 cells. European journal of cell biology 38 23102833
2019 C-reactive protein promotes inflammation through TLR4/NF-κB/TGF-β pathway in HL-1 cells. Bioscience reports 37 31391207
2014 Endoplasmic reticulum stress-mediated autophagy protects against lipopolysaccharide-induced apoptosis in HL-1 cardiomyocytes. Experimental physiology 37 24951501
2011 Doxorubicin increases oxidative metabolism in HL-1 cardiomyocytes as shown by 13C metabolic flux analysis. Toxicological sciences : an official journal of the Society of Toxicology 37 22048646
2009 Transcriptional remodeling of rapidly stimulated HL-1 atrial myocytes exhibits concordance with human atrial fibrillation. Journal of molecular and cellular cardiology 37 19615375
2017 Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes. Scientific reports 35 28871102
2008 Aldosterone induces cardiotrophin-1 expression in HL-1 adult cardiomyocytes. Endocrinology 35 18566129
2013 STIM1 participates in the contractile rhythmicity of HL-1 cells by moderating T-type Ca(2+) channel activity. Biochimica et biophysica acta 34 23458835
2005 Non-beating HL-1 cells for confocal microscopy: application to mitochondrial functions during cardiac preconditioning. Progress in biophysics and molecular biology 34 16140363
2009 Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes. Experimental biology and medicine (Maywood, N.J.) 33 19244544
2016 Glucagon-like peptide-1 regulates calcium homeostasis and electrophysiological activities of HL-1 cardiomyocytes. Peptides 32 26930508
2015 CYP-epoxygenase metabolites of docosahexaenoic acid protect HL-1 cardiac cells against LPS-induced cytotoxicity Through SIRT1. Cell death discovery 32 27182450
2013 Silencing of desmoplakin decreases connexin43/Nav1.5 expression and sodium current in HL‑1 cardiomyocytes. Molecular medicine reports 32 23877755
2011 Long-term culture of HL-1 cardiomyocytes in modular poly(ethylene glycol) microsphere-based scaffolds crosslinked in the phase-separated state. Acta biomaterialia 32 21920469
2016 Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes. Archives of biochemistry and biophysics 31 26906075
2014 FGF-23 dysregulates calcium homeostasis and electrophysiological properties in HL-1 atrial cells. European journal of clinical investigation 31 24942561
2014 Direct interaction of CaVβ with actin up-regulates L-type calcium currents in HL-1 cardiomyocytes. The Journal of biological chemistry 31 25533460
2011 ZnT-1 protects HL-1 cells from simulated ischemia-reperfusion through activation of Ras-ERK signaling. Journal of molecular medicine (Berlin, Germany) 31 22193398
2002 Transport characteristics of HL-1 cells: a new model for the study of adenosine physiology in cardiomyocytes. Biochemistry and cell biology = Biochimie et biologie cellulaire 29 12440705
2017 Environmentally Persistent Free Radicals Cause Apoptosis in HL-1 Cardiomyocytes. Cardiovascular toxicology 28 27052339
2014 Down-regulation of ATBF1 activates STAT3 signaling via PIAS3 in pacing-induced HL-1 atrial myocytes. Biochemical and biophysical research communications 28 24857987
2021 Role of the ROS-JNK Signaling Pathway in Hypoxia-Induced Atrial Fibrotic Responses in HL-1 Cardiomyocytes. International journal of molecular sciences 26 33806765
2020 Apelin-13 regulates angiotensin ii-induced Cx43 downregulation and autophagy via the AMPK/mTOR signaling pathway in HL-1 cells. Physiological research 26 32901500
2016 MitoNEET Protects HL-1 Cardiomyocytes from Oxidative Stress Mediated Apoptosis in an In Vitro Model of Hypoxia and Reoxygenation. PloS one 26 27243905
2021 ITLN1 inhibits tumor neovascularization and myeloid derived suppressor cells accumulation in colorectal carcinoma. Oncogene 25 34363021
1990 A new method for study of normal lens development in vitro using pulsatile delivery of PDGF or EGF in HL-1 serum-free medium. In vitro cellular & developmental biology : journal of the Tissue Culture Association 25 2180900
2021 Human intelectin-1 (ITLN1) genetic variation and intestinal expression. Scientific reports 24 34145348
2018 TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway. Journal of cellular and molecular medicine 24 29971943
2017 Identification of murine phosphodiesterase 5A isoforms and their functional characterization in HL-1 cardiac cell line. Journal of cellular physiology 24 28247930
2016 Colchicine modulates calcium homeostasis and electrical property of HL-1 cells. Journal of cellular and molecular medicine 24 26928894
2011 Ionic mechanisms of pacemaker activity in spontaneously contracting atrial HL-1 cells. Journal of cardiovascular pharmacology 24 20881602
2011 Metabolic flux analysis gives an insight on verapamil induced changes in central metabolism of HL-1 cells. Journal of biotechnology 24 21824500
2008 LFR, which encodes a novel nuclear-localized Armadillo-repeat protein, affects multiple developmental processes in the aerial organs in Arabidopsis. Plant molecular biology 24 18846319
2013 Distinct effects of methamphetamine on autophagy-lysosome and ubiquitin-proteasome systems in HL-1 cultured mouse atrial cardiomyocytes. Toxicology 23 23933405
2005 Attenuation of oxidative stress in HL-1 cardiomyocytes improves mitochondrial function and stabilizes Hif-1alpha. Free radical research 23 16298857
2000 Alpha-1 adrenergic signaling in a cardiac murine atrial myocyte (HL-1) cell line. Molecular and cellular biochemistry 23 11195782
2015 The ER stress-mediated mitochondrial apoptotic pathway and MAPKs modulate tachypacing-induced apoptosis in HL-1 atrial myocytes. PloS one 22 25689866
2014 AKT1 and AKT2 induce distinct phosphorylation patterns in HL-1 cardiac myocytes. Journal of proteome research 22 25162660
2012 Promoter DNA methylation regulates murine SUR1 (Abcc8) and SUR2 (Abcc9) expression in HL-1 cardiomyocytes. PloS one 22 22844491
2011 Overexpression of alternatively spliced tissue factor induces the pro-angiogenic properties of murine cardiomyocytic HL-1 cells. Circulation journal : official journal of the Japanese Circulation Society 22 21389637
2005 5-hydroxytryptamine synthesis in HL-1 cells and neonatal rat cardiocytes. Biochemical and biophysical research communications 22 15694378
2022 The Beneficial Effect of Carvacrol in HL-1 Cardiomyocytes Treated with LPS-G: Anti-Inflammatory Pathway Investigations. Antioxidants (Basel, Switzerland) 21 35204269
2000 The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT-1, AT-2 and HL-1 cardiomyocytes. Nucleic acids research 21 10908350
2012 Murine atrial HL-1 cell line is a reliable model to study drug metabolizing enzymes in the heart. Vascular pharmacology 20 23268359
2003 HL-1 myocytes exhibit PKC and K(ATP) channel-dependent delta opioid preconditioning. The Journal of surgical research 20 14559445
2019 A small-molecule LF3 abrogates β-catenin/TCF4-mediated suppression of NaV1.5 expression in HL-1 cardiomyocytes. Journal of molecular and cellular cardiology 19 31419437
2018 Inhibition of Histone Deacetylases Induces K+ Channel Remodeling and Action Potential Prolongation in HL-1 Atrial Cardiomyocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 18 30134221
2017 Uncovering the arrhythmogenic potential of TRPM4 activation in atrial-derived HL-1 cells using novel recording and numerical approaches. Cardiovascular research 18 28898995
2013 9-Phenanthrol and flufenamic acid inhibit calcium oscillations in HL-1 mouse cardiomyocytes. Cell calcium 18 23831210
2012 Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells. Channels (Austin, Tex.) 18 23018927
2023 Functional coupling between Piezo1 and TRPM4 influences the electrical activity of HL-1 atrial myocytes. The Journal of physiology 17 38098265
2012 The promotion of HL-1 cardiomyocyte beating using anisotropic collagen-GAG scaffolds. Biomaterials 17 22979989
2016 Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part II: HL-1 cytocompatibility and electrical characterizations. Journal of biomedical materials research. Part A 16 26822463
2016 Role of tumour necrosis factor-a in the regulation of T-type calcium channel current in HL-1 cells. Clinical and experimental pharmacology & physiology 16 27119319
2012 Common variants of SLAMF1 and ITLN1 on 1q21 are associated with type 2 diabetes in Indian population. Journal of human genetics 16 22277902
2012 Delineation of the effects of angiotensin type 1 and 2 receptors on HL-1 cardiomyocyte apoptosis. Apoptosis : an international journal on programmed cell death 16 22527949
2010 Lipopolysaccharides directly decrease Ca2+ oscillations and the hyperpolarization-activated nonselective cation current If in immortalized HL-1 cardiomyocytes. American journal of physiology. Cell physiology 16 20573997
2022 Characterization of an intelectin-1 (Itln1) knockout mouse model. Frontiers in immunology 15 36072603
2021 Pterostilbene Increases LDL Metabolism in HL-1 Cardiomyocytes by Modulating the PCSK9/HNF1α/SREBP2/LDLR Signaling Cascade, Upregulating Epigenetic hsa-miR-335 and hsa-miR-6825, and LDL Receptor Expression. Antioxidants (Basel, Switzerland) 15 34439528
2021 LFR Physically and Genetically Interacts With SWI/SNF Component SWI3B to Regulate Leaf Blade Development in Arabidopsis. Frontiers in plant science 15 34456957
2019 ITLN in diploid hybrid fish (Carassius auratus cuvieri ♀ × Carassius auratus red var ♂) is involved in host defense against bacterial infection. Developmental and comparative immunology 15 31626818
2018 LFR is functionally associated with AS2 to mediate leaf development in Arabidopsis. The Plant journal : for cell and molecular biology 15 29775508
2011 Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes. Toxicology and applied pharmacology 15 21320520
2015 Maintenance of HL-1 cardiomyocyte functional activity in PEGylated fibrin gels. Biotechnology and bioengineering 14 25657056
2015 Nanostructured cavity devices for extracellular stimulation of HL-1 cells. Nanoscale 14 25939765
2010 Integrin β3 prevents apoptosis of HL-1 cardiomyocytes under conditions of oxidative stress. Canadian journal of physiology and pharmacology 14 20393597
2006 Effects of hypoxia, glucose deprivation and acidosis on phosphatidylcholine synthesis in HL-1 cardiomyocytes. CTP:phosphocholine cytidylyltransferase activity correlates with sarcolemmal disruption. The Biochemical journal 14 16236026
2020 Hypoxia-induced alterations of transcriptome and chromatin accessibility in HL-1 cells. IUBMB life 13 32351020
2020 Mitoxantrone impairs proteasome activity and prompts early energetic and proteomic changes in HL-1 cardiomyocytes at clinically relevant concentrations. Archives of toxicology 13 32894303
2023 Arabidopsis LFR, a SWI/SNF complex component, interacts with ICE1 and activates ICE1 and CBF3 expression in cold acclimation. Frontiers in plant science 12 37025149
2020 LRP1-Mediated AggLDL Endocytosis Promotes Cholesteryl Ester Accumulation and Impairs Insulin Response in HL-1 Cells. Cells 12 31936892
2016 Doxazosin Stimulates Galectin-3 Expression and Collagen Synthesis in HL-1 Cardiomyocytes Independent of Protein Kinase C Pathway. Frontiers in pharmacology 12 28066244
2008 Overexpression of human truncated peroxisome proliferator-activated receptor alpha induces apoptosis in HL-1 cardiomyocytes. Cardiovascular research 12 18440986
2000 An immortalized myocyte cell line, HL-1, expresses a functional delta -opioid receptor. Journal of molecular and cellular cardiology 12 11112994
2019 Sodium hydrosulphide restores tumour necrosis factor-α-induced mitochondrial dysfunction and metabolic dysregulation in HL-1 cells. Journal of cellular and molecular medicine 11 31496037
2017 Role of the rs2274907 allelic variant of the ITLN1 gene in patients with diabetic foot. Polish archives of internal medicine 11 28442700