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EFFECT OF ALL‐TRANS RETINOIC ACID ON UNILATERAL URETERAL OBSTRUCTION MODEL

To the Editor: Renal interstitial fibrosis (RIF) plays a most important role in the progression of renal diseases to end-stage renal failure. Unilateral ureteral obstruction (UUO) model was used extensively as a model of progressive RIF, accompanied by rapid parenchymal deterioration. All-trans retinoic acid (ATRA), a natural derivative of vitamin A, plays an important role in the prevention of fibrosis. However, there was a rare report investigating the effect of ATRA on RIF. Interestingly, Kishimoto et al. performed an investigation on the association of ATRA treatment with RIF progression in UUO model mice, and found that a significant improvement was observed in histological and immunological findings in the ATRA treatment group, including macrophage infiltration and improved expression of monocyte chemotactic protein-1, transforming growth factor-b1 (TGF-b1), a-smooth muscle actin (a-SMA) and collagen I compared with the UUO model group. They drew a conclusion that ATRA treatment was not only an effective prophylactic strategy, but also a therapeutic strategy for the treatment of progressive renal fibrosis in diseased kidneys. We also performed an investigation on the association of the ATRA treatment with RIF progression. The rats were divided into three groups: sham operation group (SHO), group of UUO model (GU) and UUO model group treated with ATRA (GA). The UUO model was established, and the rats in the GA group were treated with ATRA (Sigma, St. Louis, MO, USA; 15 mg/kg per day) in corn oil once daily by oral gavage, from the first day before operation. Rats in the GU and SHO groups were administrated saline. Rats from the three groups were killed 14 and 28 days after surgery, and the renal tissue was collected for the determination of histological and molecular biology. In our study, we found that ATRA treatment could significantly reduce the expressions of TGF-b1, a-SMA, collagen IV and fibronectin. Our results were similar with those from Kishimoto et al. So, ATRA might become a useful therapeutic strategy for the treatment of progressive renal fibrosis. All-trans retinoic acid might play an important role in the administration of renal diseases in experimental studies. In our previous study, we found that ATRA could alleviate glomerulosclerosis lesion in glomerulosclerosis rats induced by adriamycin. ATRA might be a candidate drug for the treatment of renal diseases in a clinical setting. However, further investigation should be performed in experimental animal models and the effect of ATRA should be confirmed in the clinical practice.