ArticleCellular and molecular gastroenterology and hepatology2016
Inhibitors of Arg-Gly-Asp-Binding Integrins Reduce Development of Pancreatic Fibrosis in Mice.
Article in Cellular and molecular gastroenterology and hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- A Novel Insight into Chronic Pancreatitis Pathogenesis: the USP1/ITGB5 Axis-Mediated Stellate Cell Activation.Inflammation · 2026Article
- Using Integrin αInternational journal of radiation oncology, biology, physics · 2025Article
- Pancreatic stellate cells: Key players in pancreatic health and diseases (Review).Molecular medicine reports · 2024Review
- Irisin reduces the abnormal reproductive and metabolic phenotypes of PCOS by regulating the activity of brown adipose tissue in mice†.Biology of reproduction · 2022Article
- CWHM-12, an Antagonist of Integrin-Mediated Transforming Growth Factor-Beta Activation Confers Protection During EarlyJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Article
- Controllable graphene oxide-based biocompatible hybrid interface as an anti-fibrotic coating for metallic implants.Materials today. Bio · 2022Article
- Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease.JHEP reports : innovation in hepatology · 2022Review
- New Therapeutic Targets for Hepatic Fibrosis in the Integrin Family, α8β1 and α11β1, Induced Specifically on Activated Stellate Cells.International journal of molecular sciences · 2021Review
- Dark Side of Cancer Therapy: Cancer Treatment-Induced Cardiopulmonary Inflammation, Fibrosis, and Immune Modulation.International journal of molecular sciences · 2021Review
- Puerarin Ameliorates Caerulein-Induced Chronic PancreatitisFrontiers in pharmacology · 2021Article
- Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury.Physiological reports · 2020Article
- Emerging strategies to disrupt the central TGF-β axis in kidney fibrosis.Translational research : the journal of laboratory and clinical medicine · 2019Review
- An Inhibitor of Arginine-Glycine-Aspartate-Binding Integrins Reverses Fibrosis in a Mouse Model of Nonalcoholic Steatohepatitis.Hepatology communications · 2019Article
- αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.Nature communications · 2017Article
- The deubiquitylase USP10 regulates integrin β1 and β5 and fibrotic wound healing.Journal of cell science · 2017Article
- RGD-Modified Albumin Nanoconjugates for Targeted Delivery of a Porphyrin Photosensitizer.Molecular pharmaceutics · 2017Article
- Pancreatic stellate cell: Pandora's box for pancreatic disease biology.World journal of gastroenterology · 2017Review
- Article
- Targeting αv Integrins in Pancreatic Fibrosis: Progress in Resolving the Scar.Cellular and molecular gastroenterology and hepatology · 2016Article
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10 authors.
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Abstract
BACKGROUND &
aimsPancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by the cytokine transforming growth factor β (TGFB). Integrins of the αv family promote TGFB signaling in mice, probably by interacting with the Arg-Gly-Asp (RGD) sequence of the TGFB latency-associated peptide, which frees TGFB to bind its cellular receptors. However, little is known about the role of integrins in the development of CP. We investigated the effects of small-molecule integrin inhibitors in a mouse model of CP.
methodsWe induced CP in C57BL/6 female mice by repeated cerulein administration. An active RGD peptidomimetic compound (Center for World Health and Medicine [CWHM]-12) was delivered by continuous infusion, starting 3 days before or 5 days after cerulein administration began. Pancreata were collected and parenchymal atrophy, fibrosis, and activation of PSCs were assessed by histologic, gene, and protein expression analyses. We measured CWHM-12 effects on activation of TGFB in co-culture assays in which rat PSC cells (large T immortalized cells [LTC-14]) activate expression of a TGFB-sensitive promoter in reporter cells.
resultsPancreatic tissues of mice expressed messenger RNAs encoding subunits of RGD-binding integrins. Cerulein administration increased expression of these integrins, altered pancreatic cell morphology, and induced fibrosis. The integrin inhibitor CWHM-12 decreased acinar cell atrophy and loss, and substantially reduced fibrosis, activation of PSCs, and expression of genes regulated by TGFB. CWHM-12 also reduced established fibrosis in mice and blocked activation of TGFB in cultured cells.
conclusionsBased on studies of a mouse model of CP and cultured PSCs, integrins that bind RGD sequences activate PSCs and promote the development of pancreatic fibrogenesis in mice. Small-molecule antagonists of this interaction might be developed for treatment of pancreatic fibrotic diseases.
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