NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells

Atsushi Masamune, Takashi Watanabe, Kazuhiro Kikuta, Kennichi Satoh, Tooru Shimosegawa

研究成果: Article査読

99 被引用数 (Scopus)

抄録

Activated pancreatic stellate cells (PSCs) play an important role in pancreatic fibrosis and inflammation, where oxidative stress is implicated in the pathogenesis. NADPH oxidase might be a source of reactive oxygen species (ROS) in the injured pancreas. This study aimed to clarify the expression and regulation of cell functions by NADPH oxidase in PSCs. PSCs were isolated from rat and human pancreas tissues. Expression of NADPH oxidase was assessed by reverse transcription-PCR and immunostaining. Intracellular ROS production was assessed using 2′,7′-dichloro-fluorescin diacetate. The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro. In vivo, DPI (at 1 mg·kg body wt-1·day-1) was administered in drinking water to 10-wk-old male Wistar Bonn/Kobori rats for 10 wk and to rats with chronic pancreatitis induced by dibutyltin dichloride (DBTC). PSCs expressed key components of NADPH oxidase (p22phox, p47 phox, NOX1, gp91phox/NOX2, NOX4, and NOX activator 1). PDGF-BB, IL-1β, and angiotensin II induced ROS production, which was abolished by DPI and apocynin. DPI inhibited PDGF-induced proliferation, IL-1β-induced chemokine production, and expression of α-smooth muscle actin and collagen. DPI inhibited transformation of freshly isolated cells to a myofibroblast-like phenotype. In addition, DPI inhibited the development of pancreatic fibrosis in Wistar Bonn/Kobori rats and in rats with DBTC-induced chronic pancreatitis. In conclusion, PSCs express NADPH oxidase to generate ROS, which mediates key cell functions and activation of PSCs. NADPH oxidase might be a potential target for the treatment of pancreatic fibrosis.

本文言語English
ページ(範囲)G99-G108
ジャーナルAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
294
1
DOI
出版ステータスPublished - 2007

ASJC Scopus subject areas

  • 生理学
  • 肝臓学
  • 消化器病学
  • 生理学(医学)

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