Insulin-like growth factor-1 alleviates hepatocyte senescence by regulating intranuclear p53-progerin pathway

Abstract

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H(2)O(2)). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-β-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-β-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.