The role of CTGF in peritoneal fibrosis and renal-peritoneal interactions

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16080
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Toda Naohiro 京都大学, 医学研究科, 客員研究員 (30760615)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: CTGF / 腹膜透析 / 腹膜機能

Outline of Final Research Achievements

Connective tissue growth factor (CTGF) regulates the signalling of other growth factors and promotes fibrosis. CTGF is shown to be an aggravating factor in thickening peritoneum.To study the role of CTGF in peritoneal fibrosis of adult mice, we generated CTGF conditional knockout (cKO) mice. We induced peritoneal fibrosis in wild-type and Rosa-CTGF cKO mice.
Induction of peritoneal fibrosis in wild-type mice increased CTGF expression and produced severe thickening of the peritoneum. In contrast, CG-treated Rosa-CTGF cKO mice exhibited reduced thickening of the peritoneum. Peritoneal equilibration test revealed that the excessive peritoneal permeability by CG treatment was normalized by CTGF deletion. CG-treated Rosa-CTGF cKO mice exhibited a reduced number of αSMA- and Ki67-positive cells in the peritoneum. These results indicate that a deficiency of CTGF can reduce peritoneal thickening and help to maintain peritoneal function.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

腹膜透析は在宅で生活できるなどの多くの利点を有するが、腹膜線維化によって治療中止を余儀なくされることがある。腹膜線維化は腹膜透析における最も重要な合併症である。CTGFの抑制は腹膜線維化を軽減するだけでなく、腹膜機能の改善も示した。抗CTGF中和抗体は肺線維症などの分野ですでに臨床試験が行われており、他の論文ではこの中和抗体で腹膜線維化が軽減することが示されている。腹膜透析におけるCTGF抑制は臨床応用につながりうると考える。