TSP-1 promotes glomerular mesangial cell proliferation and extracellular matrix secretion in Thy-1 nephritis rats

Wen Qiu,Yan Li,Jianbo Zhou,Chenhui Zhao,Jing Zhang,Kai Shan,Dan Zhao,Yingwei Wang

doi:10.1016/s1674-8301(11)60053-5

Abstract

The proliferation of glomerular mesangial cells (GMC) and secretion of the extracellular matrix (ECM) in rat with Thy-1 nephritis (Thy-1N) resembling human mesangioproliferative glomerulonephritis have been explored for many years; however, the molecular mechanisms of GMC proliferation and ECM production remain unclear. Our previous studies have demonstrated that the thrombospondin-1 (TSP-1) gene was involved in mediating rat GMC proliferation and ECM synthesis induced by sublytic C5b-9 in vitro. In the present study, the roles of the TSP-1 gene in GMC proliferation, ECM production, and urinary protein secretion in Thy-1N rats were determined by using TSP-1 small hairpin RNA, and the results revealed that silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation ( P < 0.01) and ECM secretion ( P < 0.01) as well as urinary protein secretion ( P < 0.05) in Thy-1N rats. Together, the current findings suggested that TSP-1 gene expression was required for GMC proliferation and ECM production in Thy-1N rats.

Highlights

Mesangioproliferative glomerulonephritis is a disease with a high incidence in humans[1]
In order to explore the roles of TSP-1 gene activation in the pathological changes of Thy-1 nephritis in rats, we transfected the plasmids of shTSP-1 and shCTR respectively, into rat kidneys followed by Thy-1
The renal expression of TSP-1 protein in different groups of rats was examined on d 7 after Thy-1 nephritis induction, and the results showed that the expression of the TSP-1 gene was obviously increased in the renal tissues of Thy1 nephritis rats, and that shTSP-1 could effectively reduce the expression of TSP-1 in the renal tissues of Thy-1 nephritis rats, while shCTR had no significant effect on renal TSP-1 expression (Fig. 2)

Summary

Introduction

Mesangioproliferative glomerulonephritis is a disease with a high incidence in humans[1]. C5b-9 complexes have been shown in the glomeruli of patients with mesangioproliferative glomerulonephritis[4,5], the role of C5b-9 has not been fully understood until now. Rat Thy-1 nephritis is an animal model for human mesangioproliferative glomerulonephritis[6,7,8]. Thy-1 antibody can bind to Thy-1 antigen present on the GMC membrane, forming immune complexes, and activate the complement system, causing GMC pathological lesions[9,10]. Several reports have demonstrated that renal pathological lesions in Thy-1 nephritis are C5b-9-dependent and neutrophil-independent[6,11,12]

Methods

Results

Conclusion