Effect of V-ATPase inhibition in renal fibrosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16092
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Yabana Ikuko 東北医科薬科大学, 医学部, 助教 (60778596)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腎臓 / 線維化 / 細胞内タンパク質輸送 / 酸性オルガネラ

Outline of Final Research Achievements

The vacuolar ATPase (V-ATPase) regulates the pH of organelle vesicles and is involved in the intracellular and extracellular transport of proteins. We investigated the effect of V-ATPase inhibition on fibrosis in the kidney. First, we examined the effect of bafilomycin (BAF: V-ATPase inhibitor) on TGF-β-induced fibrosis in M1 cells derived from mouse renal cortical collecting ducts. The fibrotic proteins induced by TGF-β were trapped in the cytoplasmic organelle by V-ATPase inhibition. Next, we investigated the effect of BAF on renal fibrosis in a renal fibrosis model, UUO. Fibrosis induced by the UUO was partially inhibited in the BAF-treated group compared to the control group. However, the increase in liver weight and hepatic fibrosis were observed, meaning the hepatotoxicity was stronger than the inhibitory effect of BAF on fibrosis.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

腎線維化の進展にはV-ATPaseにより調節される細胞内酸性オルガネラを介したタンパク質輸送が関与している。障害により誘導された線維化タンパク質は、V-ATPase阻害により細胞外への輸送が抑制され、細胞内の酸性オルガネラにとどまるようになる。組織障害に伴う線維化に対し、障害を受けた組織特異的なV-ATPase阻害により線維化を抑制し、組織を保護できる可能性が示唆された。