Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis.

Abstract

BackgroundThe aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated β-galactosidase (SA-β-Gal) and its association with glomerular lesions were investigated in a mouse model of LN.Material/MethodsEighteen MRL/lpr mice with severe proteinuria were randomly divided into 2 equal groups and intraperitoneally injected with dexamethasone (DEX) or saline; 4 age-matched mice with mild proteinuria served as controls. Serum creatinine and urinary protein levels were analyzed, and kidney histological changes were observed by periodic acid–Schiff and Sirius Red staining. SA-β-Gal was detected via histochemistry. Glomerular expression of collagen IV, α-SMA, and nephrin was analyzed by immunohistochemistry, and glomerular complement C3 deposition was tested by immunofluorescence. The relationships between SA-β-Gal expression and renal function or glomerular lesion markers were determined by Spearman’s correlation analysis.ResultsMice with severe proteinuria exhibited glomerular segmental sclerosis and endothelial cell proliferation. DEX administration suppressed these lesions but had no significant effect on 24-hour urinary protein levels. The elevated glomerular expression of SA-β-Gal in proteinuric mice was attenuated by DEX treatment. In addition, DEX treatment markedly downregulated glomerular C3 deposition and collagen IV and α-SMA expression, while significantly increasing nephrin expression. Furthermore, SA-β-Gal expression was positively correlated with urinary protein levels and expression of α-SMA.ConclusionsAccelerated senescence of glomerular cells may contribute to glomerular injury in LN.