ArticlePancreas
Parathyroid Hormone-Related Protein Interacts With the Transforming Growth Factor-β/Bone Morphogenetic Protein-2/Gremlin Signaling Pathway to Regulate Proinflammatory and Profibrotic Mediators in Pancreatic Acinar and Stellate Cells.
Article in Pancreas. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature.Journal of personalized medicine · 2022Review
- Gremlin1 and TGF-β1 protect kidney tubular epithelial cells from ischemia-reperfusion injury through different pathways.International urology and nephrology · 2022Article
- Uncarboxylated osteocalcin promotes proliferation and metastasis of MDA-MB-231 cells through TGF-β/SMAD3 signaling pathway.BMC molecular and cell biology · 2022Article
- Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes.Oncology reports · 2022Article
- Physiological roles of parathyroid hormone-related protein.Acta bio-medica : Atenei Parmensis · 2019Review
- SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes.Diabetes · 2017Article
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4 authors at 2 institutions in 1 country.
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Abstract
objectivesTransforming growth factor β (TGF-β) regulates immune and fibrotic responses of chronic pancreatitis. The bone morphogenetic protein 2 (BMP-2) antagonist gremlin is regulated by TGF-β. Parathyroid hormone-related protein (PTHrP) levels are elevated in chronic pancreatitis. Here, we investigated the cross-talk between TGF-β/BMP-2/gremlin and PTHrP signaling.
methodsReverse transcription/real-time polymerase chain reaction, chromatin immunoprecipitation, Western blotting, and transient transfection were used to investigate PTHrP regulation by TGF-β and BMP-2 and gremlin regulation by PTHrP. The PTHrP antagonist PTHrP (7-34) and acinar cells with conditional Pthrp gene deletion (PTHrP) were used to assess PTHrP's role in the proinflammatory and profibrotic effects of TGF-β and gremlin.
resultsTransforming growth factor β increased PTHrP levels in acinar cells and pancreatic stellate cells (PSCs) through a Smad3-dependent pathway. Transforming growth factor β's effects on levels of IL-6 and intercellular adhesion molecule 1 (ICAM-1) (acinar cells) and procollagen I and fibronectin (PSCs) were inhibited by PTHrP (7-34). PTHrP suppressed TGF-β's effects on IL-6 and ICAM-1. Parathyroid hormone-related hormone increased gremlin in acinar cells, and inhibiting gremlin action suppressed TGF-β's and PTHrP's effects on IL-6 and ICAM-1. Transforming growth factor β-mediated gremlin up-regulation was suppressed in PTHrP cells. Bone morphogenetic protein 2 suppressed PTHrP levels in PSCs.
conclusionsParathyroid hormone-related hormone functions as a novel mediator of the proinflammatory and profibrotic effects of TGF-β. Transforming growth factor β and BMP-2 regulate PTHrP expression, and PTHrP regulates gremlin levels.
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