Haruhito Yoshimine1, Shiroh Tanoue2, Yutaro Ibi1, Masato Minami1, Mai Nakahara1, Koki Tokunaga1, Shuji Kanmura1, Akio Ido1. 1. Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. 2. Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. tanoue@m.kufm.kagoshima-u.ac.jp.
Abstract
BACKGROUND: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. METHODS: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. RESULTS: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-β, TNF-α, IL-1β) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. CONCLUSION: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.
BACKGROUND: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. METHODS: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. RESULTS: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-β, TNF-α, IL-1β) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. CONCLUSION: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.
Authors: John D Williams; Kathrine J Craig; Nicholas Topley; Christopher Von Ruhland; Maureen Fallon; Geoffrey R Newman; Ruth K Mackenzie; Geraint T Williams Journal: J Am Soc Nephrol Date: 2002-02 Impact factor: 10.121
Authors: Peter J Margetts; Philippe Bonniaud; Limin Liu; Catherine M Hoff; Clifford J Holmes; Judith A West-Mays; Margaret M Kelly Journal: J Am Soc Nephrol Date: 2004-12-08 Impact factor: 10.121
Authors: Janusz Witowski; Justyna Wisniewska; Katarzyna Korybalska; Thorsten O Bender; Andrzej Breborowicz; Gerhard M Gahl; Ulrich Frei; Jutta Passlick-Deetjen; Achim Jörres Journal: J Am Soc Nephrol Date: 2001-11 Impact factor: 10.121
Authors: Llinos W Morgan; Anders Wieslander; Malcolm Davies; Takashi Horiuchi; Yuji Ohta; M Janine Beavis; Kathryn J Craig; John D Williams; Nicholas Topley Journal: Kidney Int Date: 2003-11 Impact factor: 10.612
Authors: Ceri A Fielding; Gareth W Jones; Rachel M McLoughlin; Louise McLeod; Victoria J Hammond; Javier Uceda; Anwen S Williams; Mark Lambie; Thomas L Foster; Chia-Te Liao; Christopher M Rice; Claire J Greenhill; Chantal S Colmont; Emily Hams; Barbara Coles; Ann Kift-Morgan; Zarabeth Newton; Katherine J Craig; John D Williams; Geraint T Williams; Simon J Davies; Ian R Humphreys; Valerie B O'Donnell; Philip R Taylor; Brendan J Jenkins; Nicholas Topley; Simon A Jones Journal: Immunity Date: 2014-01-09 Impact factor: 31.745