Connexins regulate cell functions in pancreatic stellate cells

Atsushi Masamune, Noriaki Suzuki, Kazuhiro Kikuta, Hiroyuki Ariga, Shintaro Hayashi, Tetsuya Takikawa, Kiyoshi Kume, Shin Hamada, Morihisa Hirota, Atsushi Kanno, Shinichi Egawa, Michiaki Unno, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Objective: 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.

Original languageEnglish
Pages (from-to)308-316
Number of pages9
JournalPancreas
Volume42
Issue number2
DOIs
Publication statusPublished - 2013 Mar

Keywords

  • fibrosis
  • gap junction
  • myofibroblast
  • pancreatic cancer
  • pancreatitis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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