Pristimerin improve renal fibrosis by regulating miRNA-145-5p in vitro and vivo study

Chen Xiao-Mei,Yang Yan-Lang,Xu Hai-Hong,Zhang Jin-Yu,Yu Yuan-Yuan,Wang Yu-Wei

doi:10.1590/fst.79021

Abstract

Abstract Pristimerin (Pri) was a kind of extraction from natural plant, and it has anti- inflammation effects in previous studies, however, it has been unclear that Pri’s effect in renal fibrosis treatment. The purpose of this research was to evaluate pristimerin (Pri) treatment effects in renal fibrosis and relative mechanisms in vivo study. Using UUO and TGF-β1 to make renal fibrosis rats and HK-2 cell fibrosis model. Evaluating renal tissues pathological and fibrosis by HE and Masson staining; measuring Scr and BUN concentrations of serum, IL-1β, TNF-α, SOD and MDA concentrations by ELISA assay in serum and supernatant. Relative gene expressions were measured by RT-qPCR assay in renal tissues and cells and relative proteins expression by WB assay. Using Double luciferase assay to analysis correlation between miRNA-145-5p and TLR4. NF-κB(p65) nuclear volume were evaluated by cellular immunofluorescence. Scr, BUN, IL-1β, TNF-α and MDA concentrations were significantly increased and SOD concentration was significantly down-regulation (P < 0.001) in Model rats group; miRNA-145-5p gene expression was significantly depressed, TLR4, MyD88 and NF-κB(p65) gene expressions were significantly increased (P < 0.001, respectively); with Pri supplement, the renal pathological, masson region, Scr, BUN, IL-1β, TNF-α, SOD and MDA were significantly improved. In cell experiment, miRNA-145-5p play important role in Pri treatment of renal fibrosis by targeting TLR4. Pri could improve renal fibrosis by via regulation miRNA-145-5p to target TLR4.

Highlights

Renal interstitial fibrosis is a common pathway for the progression to end-stage renal disease
Multiple signaling pathways are implicated in the pathogenesis of renal interstitial fibrosis, among which TLR4/MyD88/NF-κB(p65) signaling pathway has been explored comprehensively
The results suggested that miRNA-145-5p could target TLR4 in HK-2 cells

Summary

Introduction

Renal interstitial fibrosis is a common pathway for the progression to end-stage renal disease. Multiple signaling pathways are implicated in the pathogenesis of renal interstitial fibrosis, among which TLR4/MyD88/NF-κB(p65) signaling pathway has been explored comprehensively. Activation of this signaling pathway has been reported to be intimately associated with renal interstitial fibrosis and related inflammatory response (Mahmoud et al, 2019). MicroRNAs (miRNAs) can regulate the expression of various proteins under physiological and pathological conditions (). MiRNAs are small noncoding RNA molecules containing 18-23 nucleotides that regulate protein levels through interactions with sequences in the 3’-untranslated region (3’-UTR) of target gene mRNA (Goto et al, 2016; Hou et al, 2016). MiR-145-5p belongs to miRNA family, which has been found to play an important role in inflammation and inflammation-induced organ damage (Gu et al, 2019; Zhang et al, 2019; Yan et al, 2019)

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