Kazuya Kishimoto; Koji Kinoshita; Shoichi Hino; Tomohiro Yano; Yasuaki Nagare; Hideki Shimazu; Yuji Nozaki; Masafumi Sugiyama; Shinya Ikoma; Masanori Funauchi
NEPHRON EXPERIMENTAL NEPHROLOGY 118 3 E69 - E78 2011年
Background: Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent anti-proliferative, anti-inflammatory and anti-fibrotic properties. We investigated the therapeutic effect of all-trans-retinoic acid (ATRA) on unilateral ureteral obstruction (UUO) model mice. Methods: First, to evaluate the prophylactic effect, we administered 0.5 mg of ATRA for 3 days before UUO (UUO ATRA). Then, to evaluate the therapeutic effects, we administered 0.5 mg of ATRA 3 days after UUO (Day3 ATRA). We compared the histological changes and immunostaining of macrophages, alpha-smooth muscle actin (alpha-SMA) and collagen I, and mRNA expression of monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-beta(1) and TGF-beta R-II by RT-PCR 7 days after UUO. Results: In the UUO ATRA and Day3 ATRA groups, we observed a significant improvement in histological and immunological findings, including macrophage infiltration and improved expression of MCP-1, TGF-beta(1), alpha-SMA and collagen I compared with the UUO Day7 group. Conclusion: ATRA treatment is not only an effective prophylactic strategy, but also a therapeutic strategy for the treatment of progressive renal fibrosis in diseased kidneys. Copyright (C) 2011 S. Karger AG, Basel