Human glomerular mesangial cells (HMCs) have a finite lifespan, and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders, such as chronic kidney disease. The signal transducer and activator of transcription 1 (STAT1) is a latent transcription factor involved in a variety of signal transduction pathways, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, the induction of angiotensin II (Ang II)-accelerated HMC senescence, as judged by increased senescence-associated β-galactosidase (SA-β-gal)-positive staining cells, morphological changes, and G0/G1 cell cycle arrest. STAT1 activity and the expression of p53 and p21Cip1 were increased after Ang II treatment. STAT1 knockdown using RNA interference significantly inhibited the progression of HMC senescence and decreased the elevated expression of p53 and p21Cip1. Pretreating HMCs with Ang II receptor blocker losartan also inhibited the progression of HMC senescence and STAT1 activity. Our results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21Cip1 pathway, and that losartan could attenuate HMC senescence by regulating STAT1. The antioxidant N-acetyl-L-cysteine reduced ROS production and STAT1 activity induced by Ang II, indicating that Ang II uses ROS as a second messenger to regulate STAT1 activity.
Pyk2 controls filamentous actin formation in human glomerular mesangial cells via modulation of profilin expression
