Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells.

Lupus nephritis (LN) is the most common and lethal complication of systemic lupus erythematosus. We aimed to explore the protective effect of Sirtuin1 (Sirt1) on LN by regulating the NLRP3 signaling pathway in human glomerular mesangial cells (GMCs). We collected clinical samples from patients with LN, detected Sirt1 protein and mRNA expression using biochemical methods, cultured GMCs in vitro, evaluated levels of oxidative stress, cell apoptosis, and mitochondrial damage, and analyzed the expression of NLRP3 pathway proteins. Our results demonstrated that Sirt1 protein and mRNA were downregulated in the renal tissue of LN patients, and LN serum induced an increase in oxidative stress, cell apoptosis, and mitochondrial damage in GMCs while activating the NLRP3 signaling pathway. Upregulation of Sirt1 inhibited LN serum-induced oxidative stress in GMCs, reduced the number of cell apoptosis, and stabilized mitochondrial structure and function. Moreover, Sirt1 overexpression inhibited the expression of NLRP3 pathway proteins. Our findings suggest that Sirt1 may protect LN by inhibiting the NLRP3 signaling pathway in GMCs.