Work

Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy

Year: 2025

Type: article

Abstract: Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN. • Prrx1 exhibited elevated expression levels in diabetic nephropathy, which stimulated mesangial cell proliferation. • Renal specific knockdown of Prrx1 improves renal function in diabetic nephropathy mice. • Prrx1 binds to YAP promoter to promote YAP transcription and induce mesangial cell proliferation.

Source: Journal of Pharmaceutical Analysis

DOI: 10.1016/j.jpha.2025.101247