Therapeutic effect of retinoic acid on unilateral ureteral obstruction model.

ABSTRACT

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 (Day 3 ATRA). We compared the histological changes and immunostaining of macrophages, α-smooth muscle actin (α-SMA) and collagen I, and mRNA expression of monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-ß(1) and TGF-ß R-II by RT-PCR 7 days after UUO. RESULTS: In the UUO ATRA and Day 3 ATRA groups, we observed a significant improvement in histological and immunological findings, including macrophage infiltration and improved expression of MCP-1, TGF-ß(1), α-SMA and collagen I compared with the UUO Day 7 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.