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.

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools

“…Renal diseases such as IgA nephropathy and lupus nephritis associate with increased senescent cell burden (Liu et al, 2012; Yang et al, 2018), but diabetes mellitus is the most studied disease regarding cellular senescence in the kidney.…”

Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain

“…It hydrolyzes β-galactosides to monosaccharides and the enzyme is active even at acidic pH (6.0). SA-β-gal activity has been widely used as a reliable marker of cellular senescence in brain (20)(21)(22) and other organs (23,24). In the present study, using an advanced blast simulator (ABS) to expose animals to single and tightly coupled repeated blasts, we have carried out postmortem evaluation of SA-β-gal activity in different anatomical regions of the brain at various time points up to 1 year post-blast exposures to determine whether blast exposure accelerate cellular senescence, an indicator of aging processes.…”

Cell Senescence in Lupus

“…Interestingly, evidence of senescence in the kidney can occur without evidence of telomere shortening [ 64 ]. Very recently, data shows biomarkers of cellular senescence in murine and human lupus including upregulation of SABG and p16 ink4a [ 65 ••, 66 ]. These studies have shown a potential role for wnt9a in renal cellular senescence and fibrosis [ 65 ••].…”