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STAT1 mediates cellular senescence induced by angiotensin II and H2O2 in human glomerular mesangial cells

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Abstract

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 H2O2 accelerated premature senescence of HMCs as confirmed by increased senescence-associated -β-galactosidase (SA-β-gal) positive staining cells and G0/G1 cell cycle arrest. The STAT1 and STAT3 activity and the expression of p53 and p21Cip1 were increased after Angiotensin II and H2O2 treatment. Knockdown STAT1 using RNA interference significantly attenuated the progression of HMCs senescence, decreased the elevated p53 and p21Cip1, more interestingly, STAT3 and its activity was further enhanced while STAT1 was silenced. Our results indicate that STAT1 might mediate Ang II and H2O2-induced HMCs senescence through p53/p21Cip1 pathway and the relative abundance of STAT1 and STAT3.

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Acknowledgment

This study was supported by a grant from the Major Basic Project of China (973), No.2007CB507400. The authors thank the central laboratory of First Hospital of China Medical University for valuable suggestions and help.

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping, Shenyang, 110001, Liaoning, People’s Republic of China

    Sumin Jiao, Jin Zhang, Xue Yang, Xiaoyu Zheng & Lining Wang

  2. Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, People’s Republic of China

    Fanji Meng & Xiaoyu Zheng

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  1. Sumin Jiao
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  2. Fanji Meng
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Correspondence to Lining Wang.

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Jiao, S., Meng, F., Zhang, J. et al. STAT1 mediates cellular senescence induced by angiotensin II and H2O2 in human glomerular mesangial cells. Mol Cell Biochem 365, 9–17 (2012). https://doi.org/10.1007/s11010-011-1197-3

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  • DOI: https://doi.org/10.1007/s11010-011-1197-3

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