All-Trans Retinoic Acid Treatment Is Associated with Prohibitin Expression in Renal Interstitial Fibrosis Rats

Tian-Biao Zhou,Yan-Jun Zhao,Feng-Ying Lei,Yuan-Han Qin,Hui-Ling Xu,Zheng-Yi Li

doi:10.3390/ijms13032769

Abstract

This study was performed to investigate the association of prohibitin with renal interstitial fibrosis (RIF) lesion and to explore the association of all-trans retinoic acid (ATRA) treatment with prohibitin expression in RIF rats. Rats were divided into three groups: the sham operation group (SHO), the model group subjected to unilateral ureteral obstruction (UUO), and the model group treated with ATRA (GA). Renal tissues were collected at 14 and 28 days after surgery, and the relevant indicators were detected. In comparison with the SHO group, the RIF index in the UUO group was markedly elevated (p < 0.01), and the RIF index in the GA group was alleviated compared with that in the UUO group (p < 0.01). Compared with the SHO group, the expression of prohibitin (protein or mRNA) in the UUO group was significantly reduced (each p < 0.01). Prohibitin expression in the GA group was markedly increased when compared with that in the UUO (p < 0.01). The expression of TGF-β1 (protein and mRNA), protein expressions of Col-IV, fibronectin, α-SMA and cleaved Caspase-3, ROS generation and cell apoptosis index in the UUO group were markedly higher than those in the SHO group (all p < 0.01), and their expressions in the GA group were markedly down-regulated compared to those in the UUO group (all p < 0.01, respectively). The protein expression of prohibitin was negatively correlated with the RIF index, protein expression of TGF-β1, Col-IV, fibronectin, α-SMA or cleaved Caspase-3, ROS generation and the cell apoptosis index (each p < 0.01). In conclusion, lower expression of prohibitin is associated with the RIF, and ATRA treatment is associated with increased prohibitin, which can prevent the progression of RIF.

Highlights

Renal interstitial fibrosis (RIF) is the final common pathway leading to chronic kidney diseases and end-stage renal disease [1,2], and its effective therapeutic strategy is wanting at present
renal interstitial fibrosis (RIF), and all-trans retinoic acid (ATRA) treatment is associated with increased prohibitin, which can prevent the progression of RIF
We found that the expressions of TGF-β1, α-Smooth Muscle Actin (α-SMA), Col-IV and fibronectin in the ureteral obstruction (UUO)

Summary

Introduction

Renal interstitial fibrosis (RIF) is the final common pathway leading to chronic kidney diseases and end-stage renal disease [1,2], and its effective therapeutic strategy is wanting at present. Investigations have found that the reactive oxidative species (ROS) can contribute to the progression of renal disease induced by UUO [5,6]. Prohibitin is a ubiquitous protein with a number of different molecular functions [7] and it is mainly located on the inner mitochondrial membrane and nuclei [8]. It plays a pivotal role in the processes of cell differentiation and apoptosis [9]. The over-expression of prohibitin could protect the mitochondria from ROS-induced injury [10].

Methods

Results

Conclusion