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28 September 2018 : Animal Research  

Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis

Chen Yang1AE, Jing Xue1BCD, Ning An1ADE, Xi-jie Huang1BD, Zhi-hong Wu1D, Lin Ye1F, Zhi-hang Li1E, Shu-jun Wang1F, Qing-jun Pan1E, Dong Liang1E, Hua-feng Liu1AEFG

DOI: 10.12659/MSM.909353

Med Sci Monit 2018; 24: ANS6882-6891

Abstract

BACKGROUND: The 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 AND METHODS: Eighteen 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.

RESULTS: Mice 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.

CONCLUSIONS: Accelerated senescence of glomerular cells may contribute to glomerular injury in LN.

Keywords: Cell Aging, Dexamethasone, Glomerulonephritis, lupus nephritis, Podocytes

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750