All-Trans Retinoic Acid Attenuates the Renal Interstitial Fibrosis Lesion in Rats but Not By Transforming Growth Factor-β1/Smad3 Signaling Pathway

Abstract

All-trans retinoic acid (ATRA) is an important therapeutic agent for prevention of the renal diseases. Transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway is a key signaling pathway which takes part in the progression of renal interstitial fibrosis (RIF). This investigation was performed to study the effect of ATRA in RIF rats and its effect on the TGF-β1/Smad3 signaling pathway. Sixty Wistar male rats were divided into three groups at random: sham operation group (SHO), model group subjected to unilateral ureteral obstruction (GU), model group treated with ATRA (GA), n = 20, respectively. RIF index, protein expression of TGF-β1, collagen-IV (Col-IV) and fibronectin (FN) in renal interstitium, and mRNA and protein expressions of Smad3 in renal tissue were detected at 14-day and 28-day after surgery. The RIF index was markedly elevated in group GU than in SHO group (p < 0.01), and the RIF index of GA group was alleviated when compared with that in GU group (p < 0.01). Compared with in group SHO, the mRNA/protein expression of Smad3 in renal tissue was significantly increased in group GU (p < 0.01). However, the mRNA and protein expressions of Smad3 in renal tissue in GA group were not markedly alleviated by ATRA treatment when compared with those in GU (each p > 0.05). Protein expressions of TGF-β1, Col-IV, and FN in GU group were markedly increased than those in SHO group (each p < 0.01), and their expressions in GA group were markedly down-regulated by ATRA treatment than those of GU group (all p < 0.01). The protein expression of Smad3 was positively correlated with RIF index, protein expression of TGF-β1, Col-IV or FN (each p < 0.01). In conclusion, ATRA treatment can alleviate the RIF progression in UUO rats. However, ATRA cannot affect the signaling pathway of TGF-β1/Smad3 in the progression of RIF.

• all-trans retinoic acid
• transforming growth factor-β1
• Smad3
• extracellular matrix
• unilateral ureteral obstruction

ACKNOWLEDGMENTS

This study was supported by the Nature Science Foundation of China (no. 81060061), the Natural Science Foundation of the Guangxi Zhuang Autonomous Region (no. 0832121) and the Health Department of Guangxi Zhuang Autonomous Region (no. 200917). The authors would like to gratefully acknowledge the most helpful comments on this article received from Professor Liang Rong, Department of Pediatric-Neonatology, Baylor College of Medicine, Houston, Texas, USA.

Conflicts of Interest: The authors declare that they have no conflict of interest.

Author contributions: Tian-Biao Zhou and Yuan-Han Qin conceived and designed the experiments; Zheng-Yi Li, Li-Na Su, Tian-Biao Zhou, Yuan-Han Qin, and Hui-Ling Xu performed the experiments; Tian-Biao Zhou, Li-Na Su, and Feng-Ying Lei analyzed the data; Yuan-Han Qin contributed reagents/materials/analysis tools; and Zheng-Yi Li and Tian-Biao Zhou wrote the paper.