PMID- 22889984 OWN - NLM STAT- MEDLINE DCOM- 20130722 LR - 20191224 IS - 1536-4828 (Electronic) IS - 0885-3177 (Linking) VI - 42 IP - 2 DP - 2013 Mar TI - Connexins regulate cell functions in pancreatic stellate cells. PG - 308-16 LID - 10.1097/MPA.0b013e31825c51d6 [doi] AB - OBJECTIVES: Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with chronic pancreatitis and pancreatic cancer. Connexins (Cxs) allow direct intercellular communications as components of gap junction but also play important roles in the regulation of cell proliferation, cell differentiation, and tissue development. We here examined the expression of Cxs and Cx-mediated regulation of cell functions in PSCs. METHODS: Human PSCs were isolated from patients undergoing operation for chronic pancreatitis or pancreatic cancer. The expression of Cxs was examined by reverse transcription polymerase chain reaction, Western blotting, and immunofluorescent staining. The roles of Cxs in PSC functions were examined by using carbenoxolone, a broad-spectrum Cx inhibitor, and small interfering RNA for Cx43. RESULTS: Human activated PSCs expressed a variety of Cxs including Cx43 both in vitro and in vivo. Carbenoxolone inhibited platelet-derived growth factor-BB-induced proliferation and migration, and type I collagen expression in PSCs. In addition, carbenoxolone inhibited the activation of quiescent PSCs to a myofibroblastlike phenotype. Decreased Cx43 expression by small interfering RNA resulted in decreased proliferation and type I collagen expression. CONCLUSIONS: Pancreatic stellate cells expressed a variety of Cxs. Connexins, especially Cx43, might regulate the cell functions and activation of PSCs. FAU - Masamune, Atsushi AU - Masamune A AD - Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. amasamune@med.tohoku.ac.jp FAU - Suzuki, Noriaki AU - Suzuki N FAU - Kikuta, Kazuhiro AU - Kikuta K FAU - Ariga, Hiroyuki AU - Ariga H FAU - Hayashi, Shintaro AU - Hayashi S FAU - Takikawa, Tetsuya AU - Takikawa T FAU - Kume, Kiyoshi AU - Kume K FAU - Hamada, Shin AU - Hamada S FAU - Hirota, Morihisa AU - Hirota M FAU - Kanno, Atsushi AU - Kanno A FAU - Egawa, Shinichi AU - Egawa S FAU - Unno, Michiaki AU - Unno M FAU - Shimosegawa, Tooru AU - Shimosegawa T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pancreas JT - Pancreas JID - 8608542 RN - 0 (Collagen Type I) RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (GJA1 protein, human) RN - 0 (Gja1 protein, rat) RN - 0 (Proto-Oncogene Proteins c-sis) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 1B56C968OA (Becaplermin) RN - MM6384NG73 (Carbenoxolone) SB - IM MH - Animals MH - Becaplermin MH - Blotting, Western MH - Carbenoxolone/pharmacology MH - Cell Movement MH - Cell Proliferation MH - Cells, Cultured MH - Collagen Type I/metabolism MH - Connexin 43/metabolism MH - Connexins/antagonists & inhibitors/genetics/*metabolism MH - Dose-Response Relationship, Drug MH - Fibrosis MH - Fluorescent Antibody Technique MH - Humans MH - Male MH - Myofibroblasts/metabolism/pathology MH - Pancreatic Neoplasms/genetics/*metabolism/pathology MH - Pancreatic Stellate Cells/drug effects/*metabolism/pathology MH - Pancreatitis, Chronic/genetics/*metabolism/pathology MH - Proto-Oncogene Proteins c-sis/metabolism MH - RNA Interference MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/metabolism MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2012/08/15 06:00 MHDA- 2013/07/23 06:00 CRDT- 2012/08/15 06:00 PHST- 2012/08/15 06:00 [entrez] PHST- 2012/08/15 06:00 [pubmed] PHST- 2013/07/23 06:00 [medline] AID - 10.1097/MPA.0b013e31825c51d6 [doi] PST - ppublish SO - Pancreas. 2013 Mar;42(2):308-16. doi: 10.1097/MPA.0b013e31825c51d6.