Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis

• Published in: Gut Vol. 52; no. 10; pp. 1487 - 1493
• Main Authors: Ohnishi, N, Miyata, T, Ohnishi, H, Yasuda, H, Tamada, K, Ueda, N, Mashima, H, Sugano, K
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.10.2003; BMJ; BMJ Publishing Group LTD; Copyright 2003 by Gut
• Subjects: Actins - analysis; activin A; Activin Receptors, Type I - analysis; Activin Receptors, Type I - genetics; Activin Receptors, Type II - analysis; Activin Receptors, Type II - genetics; Activins - analysis; Activins - metabolism; Activins - pharmacology; Animals; Autocrine Communication; Biological and medical sciences; Blotting, Western - methods; Cells, Cultured; Collagen; Collagen - metabolism; Cytokines; Dose-Response Relationship, Drug; Extracellular matrix; Fibrosis; follistatin; Follistatin - pharmacology; Follistatin - therapeutic use; GAPDH; Gastroenterology. Liver. Pancreas. Abdomen; glyceraldehyde-3-phosphate dehydrogenase; Growth factors; hepatic stellate cell; HSC; Immunoglobulins; Inhibin-beta Subunits - analysis; Inhibin-beta Subunits - metabolism; Inhibin-beta Subunits - pharmacology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Microscopy; Microscopy, Fluorescence; Other diseases. Semiology; Pancreas; Pancreas - chemistry; Pancreas - drug effects; Pancreas - metabolism; pancreatic fibrosis; pancreatic stellate cell; Proteins; PSC; Rats; Reverse Transcriptase Polymerase Chain Reaction; reverse transcription-polymerase chain reaction; RNA, Messenger - analysis; Rodents; RT-PCR; TGF-β; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - pharmacology; transforming growth factor β; Transgenic animals; α smooth muscle actin; α-SMA; California; Spider cell; Follistatin; Rat; Rodentia; Gene expression; Biological activity; Vertebrata; Mammalia; Messenger RNA; Animal; Fibrosis; Digestive diseases; Molecular biology; Activin; Immunofluorescence; Pancreas; Reverse transcription polymerase chain reaction; Pancreatic disease
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.52.10.1487

Background and aim: The present study was conducted to examine the effect of activin A on activation of rat pancreatic stellate cells (PSCs). Methods: PSCs were prepared from rat pancreas using collagenase digestion and centrifugation with Nycodenz gradient. Activation of PSCs was examined by determining smooth muscle actin expression with western blotting. The presence of activin A receptors in PSCs was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunocytochemistry. Expression of activin A and transforming growth factor β (TGF-β) mRNA was examined by RT-PCR. Activin A and TGF-β peptide concentrations were examined with ELISA. Existence of activin A peptide in PSCs was investigated by immunocytochemistry. Collagen secretion was determined by Sirius red dye binding. Results: Activin A receptors I and IIa were present in PSCs. PSCs expressed activin A mRNA and secreted activin A. Activin A enhanced PSC activation and collagen secretion in a dose dependent manner. TGF-β and activin A increased each other’s secretion and mRNA expression of PSCs. Follistatin decreased TGF-β mRNA expression and TGF-β secretion of PSCs, and inhibited both PSC activation and collagen secretion. Conclusion: Activin A is an autocrine activator of PSCs. Follistatin can inhibit PSC activation and collagen secretion by blocking autocrined activin A and decreasing TGF-β expression and secretion of PSCs.