Alpha-1-antichymotrypsin: a potential inducer for epithelial-mesenchymal transition in lupus nephritis.

Abstract

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus and represents a major risk factor for mortality. The critical pathological process affecting the renal parenchyma is fibrosis, which ultimately progresses to end-stage kidney disease. Identifying the molecular mediators of fibrosis is crucial for developing novel therapeutic strategies for lupus patients. Herein, we demonstrate that alpha-1-antichymotrypsin (AACT) is a critical inducer of the epithelial-mesenchymal transition (EMT) in HK-2 cells. Immunohistochemical analysis reveal that AACT expression progressively increases with advancing LN class. We next generate AACT knockout (AACT^KO) and overexpressing (AACT^OE) HK-2 cell lines. Our results indicate that AACT levels are positively correlated with cellular migration, the expression of migration-associated proteases, and collagen secretion in HK-2 cells. Notably, AACT inhibits the expression of the epithelial marker E-cadherin while promoting that of the mesenchymal marker α-SMA. Therefore, these findings suggest that AACT may contribute to renal fibrosis via triggering EMT, thereby promoting cell migration and collagen accumulation within renal tissues. Our study identifies AACT as a potential therapeutic target to counteract LN-associated renal fibrosis.