Therapeutic effect of retinoic acid on unilateral ureteral obstruction model

Nephron Exp Nephrol. 2011;118(3):e69-78. doi: 10.1159/000322409. Epub 2011 Jan 13.

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)-β(1) and TGF-β 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-β(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.

MeSH terms

  • Actins / biosynthesis
  • Animals
  • Chemokine CCL2 / biosynthesis
  • Collagen Type I / biosynthesis
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Kidney Diseases / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / biosynthesis
  • Tretinoin / therapeutic use*
  • Ureteral Obstruction / drug therapy*
  • Ureteral Obstruction / pathology

Substances

  • Actins
  • Chemokine CCL2
  • Collagen Type I
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Tretinoin