Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis
Abstract Peritoneal fibrosis (PF) is a serious complication in various clinical settings, but the mechanisms driving it remain to be fully determined. Connective tissue growth factor (CTGF) is known to regulate fibroblast activities. We therefore examined if CTGF inhibition has anti-fibrotic effects...
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Nature Portfolio
2017
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oai:doaj.org-article:7050ef58788c4ff3a1746051cc45f7fa2021-12-02T11:50:55ZInhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis10.1038/s41598-017-05624-22045-2322https://doaj.org/article/7050ef58788c4ff3a1746051cc45f7fa2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05624-2https://doaj.org/toc/2045-2322Abstract Peritoneal fibrosis (PF) is a serious complication in various clinical settings, but the mechanisms driving it remain to be fully determined. Connective tissue growth factor (CTGF) is known to regulate fibroblast activities. We therefore examined if CTGF inhibition has anti-fibrotic effects in PF. PF was induced by repetitive intraperitoneal injections of chlorhexidine gluconate (CG) in mice with type I pro-collagen promoter-driven green fluorescent protein (GFP) expression to identify fibroblasts. FG-3019, an anti-CTGF monoclonal antibody, was used to inhibit CTGF. CG-induced PF was significantly attenuated in FG-3019-treated mice. CG challenges induced marked accumulations of proliferating fibroblasts and of myofibroblasts, which were both reduced by FG-3019. Levels of peritoneal CTGF expression were increased by CG challenges, and suppressed in FG-3019-treated mice. FG-3019 treatment also reduced the number of CD31+ vessels and VEGF-A-positive cells in fibrotic peritoneum. In vitro studies using NIH 3T3 fibroblasts and peritoneal mesothelial cells (PMCs) showed that CTGF blockade suppressed TGF-β1-induced fibroblast proliferation and myofibroblast differentiation, PMC mesothelial-to-mesenchymal transition, and VEGF-A production. These findings suggest that the inhibition of CTGF by FG-3019 might be a novel treatment for PF through the regulation of fibroblast and myofibroblast accumulation and angiogenesis.Norihiko SakaiMiki NakamuraKenneth E. LipsonTaito MiyakeYasutaka KamikawaAkihiro SagaraYasuyuki ShinozakiShinji KitajimaTadashi ToyamaAkinori HaraYasunori IwataMiho ShimizuKengo FuruichiShuichi KanekoAndrew M. TagerTakashi WadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Norihiko Sakai Miki Nakamura Kenneth E. Lipson Taito Miyake Yasutaka Kamikawa Akihiro Sagara Yasuyuki Shinozaki Shinji Kitajima Tadashi Toyama Akinori Hara Yasunori Iwata Miho Shimizu Kengo Furuichi Shuichi Kaneko Andrew M. Tager Takashi Wada Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| description |
Abstract Peritoneal fibrosis (PF) is a serious complication in various clinical settings, but the mechanisms driving it remain to be fully determined. Connective tissue growth factor (CTGF) is known to regulate fibroblast activities. We therefore examined if CTGF inhibition has anti-fibrotic effects in PF. PF was induced by repetitive intraperitoneal injections of chlorhexidine gluconate (CG) in mice with type I pro-collagen promoter-driven green fluorescent protein (GFP) expression to identify fibroblasts. FG-3019, an anti-CTGF monoclonal antibody, was used to inhibit CTGF. CG-induced PF was significantly attenuated in FG-3019-treated mice. CG challenges induced marked accumulations of proliferating fibroblasts and of myofibroblasts, which were both reduced by FG-3019. Levels of peritoneal CTGF expression were increased by CG challenges, and suppressed in FG-3019-treated mice. FG-3019 treatment also reduced the number of CD31+ vessels and VEGF-A-positive cells in fibrotic peritoneum. In vitro studies using NIH 3T3 fibroblasts and peritoneal mesothelial cells (PMCs) showed that CTGF blockade suppressed TGF-β1-induced fibroblast proliferation and myofibroblast differentiation, PMC mesothelial-to-mesenchymal transition, and VEGF-A production. These findings suggest that the inhibition of CTGF by FG-3019 might be a novel treatment for PF through the regulation of fibroblast and myofibroblast accumulation and angiogenesis. |
| format |
article |
| author |
Norihiko Sakai Miki Nakamura Kenneth E. Lipson Taito Miyake Yasutaka Kamikawa Akihiro Sagara Yasuyuki Shinozaki Shinji Kitajima Tadashi Toyama Akinori Hara Yasunori Iwata Miho Shimizu Kengo Furuichi Shuichi Kaneko Andrew M. Tager Takashi Wada |
| author_facet |
Norihiko Sakai Miki Nakamura Kenneth E. Lipson Taito Miyake Yasutaka Kamikawa Akihiro Sagara Yasuyuki Shinozaki Shinji Kitajima Tadashi Toyama Akinori Hara Yasunori Iwata Miho Shimizu Kengo Furuichi Shuichi Kaneko Andrew M. Tager Takashi Wada |
| author_sort |
Norihiko Sakai |
| title |
Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| title_short |
Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| title_full |
Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| title_fullStr |
Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| title_full_unstemmed |
Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| title_sort |
inhibition of ctgf ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/7050ef58788c4ff3a1746051cc45f7fa |
| work_keys_str_mv |
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1718395171137126400 |