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Mol Med Rep. 2011 Mar-Apr;4(2):255-60. doi: 10.3892/mmr.2011.436. Epub 2011 Jan 25.

Change of telomere length in angiotensin II-induced human glomerular mesangial cell senescence and the protective role of losartan.

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  • 1Department of Nephropathy, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Abstract

Telomeres are DNA repeats at the ends of linear chromosomes in eukaryotic cells; they form cap-like specialized structures at chromosome ends to protect them from digestion and degradation. With each cell division, somatic cell telomeres progressively wear and shorten, leading to cell senescence. Various environmental factors, such as oxidative stress and inflammation, can accelerate telomere shortening. The renin angiotensin system seems to be the key mechanism involved in aging. Our previous studies demonstrated that treatment of human glomerular mesangial cells (GMCs) with angiotensin II (AngII) caused cell senescence. It is important to understand whether AngII accelerates telomere shortening in GMCs and further promotes aging. Therefore, this study was designed to investigate the change in telomere length in AngII-induced GMC senescence and the role of the AngII receptor antagonist losartan in delaying this process. The cells were synchronized and divided into a normal control group, an AngII group (AngII, 10⁻⁶ mol/l) and an AngII + losartan group (losartan, 10⁻⁵ mol/l), and were then cultured for 72 h. The telomere lengths were analyzed by Southern blot analysis, cell morphology was monitored, the cell cycle and β-galactosidase staining were determined, and the expression of P53 and P21 proteins was assessed by Western blotting. Compared with the control group, the AngII group exhibited a markedly reduced telomere length, cell cycle arrest, enhanced β-galactosidase staining, and elevated expression of P53 and P21. The AngII + losartan group displayed longer telomere lengths, further reduced β-galactosidase staining and decreased P53 and P21 expression compared to the AngII group. This study confirms that AngII induces the shortening of telomere lengths, P53 and P21 expression, cell cycle arrest, and the resulting cell senescence in GMCs. In addition, losartan significantly reduced telomere shortening and cell senescence.

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