Shenkang Injection, a Modern Preparation of Chinese Patent Medicine, Diminishes Tubulointerstitial Fibrosis in Obstructive Nephropathy Via Targeting Pericyte-myofibroblast Transition

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2019 May 21

PMID 31105812

Citations 13

Authors

Yinglu Liu

Ge Shi

Hongyun Yee

Wenwen Wang

Wenbei Han

Buhui Liu

Wei Wu

Yue Tu

Qian Ma

Dongqin Huo

Ziyue Wan

Dongwei Cao

Yigang Wan

Affiliations

Soon will be listed here.

Abstract

Shenkang injection (SKI), a modern preparation of Chinese patent medicine, has been widely applied to clinical therapy in the chronic renal failure patients. However, it remains elusive whether SKI can ameliorate tubulointerstitial fibrosis (TIF) . Recently, pericyte-myofibroblast transition (PMT) plays an important role in the pathogenesis of TIF in obstructive nephropathy (ON). This report thus aims to demonstrate the therapeutic mechanisms of the dose-effects of SKI on TIF by targeting PMT and its signaling activation, compared with imatinib. All rats were divided into 5 groups, the sham-operated group, the vehicle-intervened group, the high dose of SKI-treated group, the low dose of SKI-treated group and the imatinib-treated group. The ON model rats were induced by unilateral ureteral obstruction (UUO), and administered with either the different doses of SKI or imatinib before and after modeling and for a period of 4 weeks. The changes before and after drugs intervention in TIF and PMT markers, and in platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways activation in the kidneys were analyzed, respectively. As a result, PMT trigger was persistently accompanied with TIF exasperation in the obstructed kidneys after UUO, and that SKI definitely targeted PMT and significantly diminished TIF . In addition, the high dose of SKI, superior to imatinib, specifically blocked PMT through inhibiting the activation of PDGFR and VEGFR signaling in the kidneys of the UUO model rats. Overall, these findings may further suggest that targeting PMT can provide new strategies for ON treatment.

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