Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats

Qi,Fang-Hua; Cai,Ping-Ping; Liu,Xiang; Si,Guo-Min

doi:10.3892/ijmm.2018.3485

Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats

Authors:
- Fang-Hua Qi
- Ping-Ping Cai
- Xiang Liu
- Guo-Min Si
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Affiliations: Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: February 12, 2018 https://doi.org/10.3892/ijmm.2018.3485
Pages: 3015-3023

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Abstract

Epithelial-mesenchymal transition (EMT) is a critical step and key factor during renal fibrosis. Preventing renal tubular EMT is important for delaying the progression of chronic kidney disease (CKD). P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. However, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown. In the present study, we examined the effect of P311 on transforming growth factor-β1 (TGF-β1)-mediated EMT in a rat model of unilateral ureteral occlusion (UUO) renal fibrosis. The recombinant adenovirus p311 (also called Ad-P311) was constructed and transferred it into UUO rats, the preventive effect and possible mechanism of P311 on TGF-β1-mediated EMT were explored. The UUO model was established successfully and Ad-P311 was administered into UUO rats each week for 4 weeks, then the serum levels of Cr, blood urea nitrogen (BUN) and albumin (ALB) were evaluated. H&E staining and Masson staining were performed to observe the pathological changes of kidneys. Immunohistochemical staining and western blot analysis were used to examine the EMT markers [E-cadherin and α-smooth muscle actin (α-SMA)], and signal transducers (p-Smad2/3 and Smad7). Integrin linked kinase (ILK) as a keyintracellular mediator that controls TGF-β1-mediated-EMT was also assayed by western blot analysis. The results showed that P311 could alleviate renal tubular damage and interstitial fibrosis improving Cr, BUN and ALB serum levels in UUO kidneys. Furthermore, P311 attenuated TGF-β1-mediated EMT through Smad-ILK signaling pathway with an increase in α-SMA, pSmad2/3 and ILK expression, and a decrease in E-cadherin and Smad7 expression in UUO kidneys. In conclusion, P311 may be involved in the pathogenesis of renal fibrosis by blocking TGF-β1-mediated EMT via TGF-β1-Smad-ILK pathway in UUO kidneys. P311 may be a novel target for the control of renal fibrosis and the progression of CKD.

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