Dataset Information

Parathyroid Hormone-Related Protein Interacts With the Transforming Growth Factor-?/Bone Morphogenetic Protein-2/Gremlin Signaling Pathway to Regulate Proinflammatory and Profibrotic Mediators in Pancreatic Acinar and Stellate Cells.

ABSTRACT: Transforming growth factor ? (TGF-?) regulates immune and fibrotic responses of chronic pancreatitis. The bone morphogenetic protein 2 (BMP-2) antagonist gremlin is regulated by TGF-?. Parathyroid hormone-related protein (PTHrP) levels are elevated in chronic pancreatitis. Here, we investigated the cross-talk between TGF-?/BMP-2/gremlin and PTHrP signaling.Reverse transcription/real-time polymerase chain reaction, chromatin immunoprecipitation, Western blotting, and transient transfection were used to investigate PTHrP regulation by TGF-? 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-? and gremlin.Transforming growth factor ? increased PTHrP levels in acinar cells and pancreatic stellate cells (PSCs) through a Smad3-dependent pathway. Transforming growth factor ?'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-?'s effects on IL-6 and ICAM-1. Parathyroid hormone-related hormone increased gremlin in acinar cells, and inhibiting gremlin action suppressed TGF-?'s and PTHrP's effects on IL-6 and ICAM-1. Transforming growth factor ?-mediated gremlin up-regulation was suppressed in PTHrP cells. Bone morphogenetic protein 2 suppressed PTHrP levels in PSCs.Parathyroid hormone-related hormone functions as a novel mediator of the proinflammatory and profibrotic effects of TGF-?. Transforming growth factor ? and BMP-2 regulate PTHrP expression, and PTHrP regulates gremlin levels.

SUBMITTER: Bhatia V

PROVIDER: S-EPMC4833530 | biostudies-literature | 2016 May-Jun

REPOSITORIES: biostudies-literature

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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.

Bhatia Vandanajay V Cao Yanna Y Ko Tien C TC Falzon Miriam M

Pancreas 20160501 5

<h4>Objectives</h4>Transforming 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.<h4>Methods</h4>Reverse transcription/real-time polymerase chain reaction, chromatin immunoprecipitation, Western blotting ...[more]

PMID: 26495794

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Dataset Information

Parathyroid Hormone-Related Protein Interacts With the Transforming Growth Factor-?/Bone Morphogenetic Protein-2/Gremlin Signaling Pathway to Regulate Proinflammatory and Profibrotic Mediators in Pancreatic Acinar and Stellate Cells.

Publications

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.

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