speculated that the mechanism was as follows: The PHB


speculated that the mechanism was as follows: The PHB expression in the GU group was weakened, which induced the generation of ROS. The increased ROS might upregulate the expression of TGF-βl.48,49 The disorder of TGF-βl might induce the expressions of Col-IV and FN,50–52 and the overexpression TGF-βl could upregulate the expression of Caspase-3.53–55 The increased Caspase-3 was associated with cell apoptosis.37,38 So, the over-accumulation of ECM was observed and index of RIF and the number of apoptotic cells were increased. Interestingly, in our investigation, we found that PHB and Caspase-3 mainly located in RTEC, and the apoptotic cell was mainly derived from RTEC. We speculated that the injury of RTEC was an early event and might play a pivotal role in the progression of RIF in UUO rats. So, how to protect the RTEC against injury was very important in the prevention Pirfenidone mouse of RIF. More attention should be paid to the event of impaired RTEC in future study. Furthermore, in our study, we also found that the PHB mainly located in RTEC, and there was only a minimal expression in mesangial cells of glomerulus. The PHB expression in glomerulus was markedly weak when compared that in renal interstitium in UUO rats (figure and data not shown). The location of PHB was similar to that in Guo et al.18 It might give us some new

insights to explore the association of PHB with renal disease. However, there was Panobinostat chemical structure Nintedanib (BIBF 1120) a limitation in our study. In this observational study, we only found that the PHB was associated with caspase-3 expression/cell apoptosis. Cell culture using RTEC

in vitro and transfection with small inhibitory RNA of PHB to decrease the PHB gene expression might be needed in future to investigate the effect of PHB on caspase-3/cell apoptosis in UUO rats. In conclusion, less expression of PHB was associated with the increased expression of Caspase-3/cell apoptosis in RIF rats, although the detailed mechanisms were not fully elucidated. So, how to upregulate the expression of PHB is very important for prevention of RIF, and PHB might be a potential therapeutic target for prevention of the cell injury. However, cells culture in RTEC and so on, and inhibition of signalling pathway of PHB need to be conducted to explore its detailed mechanism in the further. 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 paper received from Professor Liang Rong, Department of Pediatric-Neonatology, Baylor College of Medicine, Houston, Texas, USA.

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