6772

STAT1

signal transducer and activator of transcription 1, 91kDa;STAT1;signal transducer and activator of transcription 1, 91kDa

signal transducer and activator of transcription 1, 91kD|signal transducer and activator of transcription 1-alpha/beta|signal transducer and activator of transcription-1|transcription factor ISGF-3 components p91/p84

2q32.2

protein-coding

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 aging 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 HMCs senescence still remains to be explored. In our study, induction of Angiotensin II (Ang II) and H(2)O(2) accelerated premature senescence of HMCs as confirmed by increased senescence-associated -beta-galactosidase (SA-beta-gal) positive staining cells and G0/G1 cell cycle arrest. The STAT1 and STAT3 activity and the expression of p53 and p21(Cip1) were increased after Angiotensin II and H(2)O(2) treatment. Knockdown STAT1 using RNA interference significantly attenuated the progression of HMCs senescence, decreased the elevated p53 and p21(Cip1), more interestingly, STAT3 and its activity was further enhanced while STAT1 was silenced. Our results indicate that STAT1 might mediate Ang II and H(2)O(2)-induced HMCs senescence through p53/p21(Cip1) pathway and the relative abundance of STAT1 and STAT3.

Human 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 JAK2-STAT pathway plays a pivotal role in transmitting cytokine signals, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, tert-butyl hydroperoxide (tBHP)-induced cells accelerated HMC senescence, as judged by increased senescence-associated beta-galactosidase stained positive cells, morphological changes, and G0-G1 cell cycle arrest. STAT1 and STAT3 activity were increased in tBHP-induced cells. After tBHP treatment, Bcl-2 protein expression decreased and Bax protein expression increased. Blocking the JAK2-STAT pathway with AG490 and using probucol significantly inhibited the progression of HMC senescence. Bax protein expression decreased, but Bcl-2 protein expression increased after AG490 and probucol treatment. Our results indicated that the JAK2-STAT pathway might mediate tBHP-induced HMC senescence through the Bcl-2-Bax pathway, and that probucol could attenuate HMC senescence by regulating STATs.