Loss of integrin αvβ8 in murine hepatocytes accelerates liver regeneration.

Loss of integrin αvβ8 in murine hepatocytes accelerates liver regeneration. Am J Pathol. 2018 Nov 15;: Authors: Greenhalgh SN, Matchett KP, Taylor RS, Huang K, Li JT, Saeteurn K, Donnelly MC, Simpson EE, Pollack JL, Atakilit A, Simpson KJ, Maher JJ, Iredale JP, Sheppard D, Henderson NC Abstract Recent fate-mapping studies in mice have provided substantial evidence that mature adult hepatocytes are a major source of new hepatocytes following liver injury. In other systems, integrin αvβ8 has a major role in activating transforming growth factor beta (TGFβ), a potent inhibitor of hepatocyte proliferation. We hypothesized that depletion of hepatocyte integrin αvβ8 would increase hepatocyte proliferation and accelerate liver regeneration following injury. Using Itgb8flox/flox;Alb-Cre mice to deplete hepatocyte αvβ8, following partial hepatectomy, hepatocyte proliferation and liver-to-body weight ratio were significantly increased in Itgb8flox/flox;Alb-Cre mice compared to control. Antibody-mediated blockade of hepatocyte αvβ8 in vitro, with assessment of TGFβ signaling pathways by qPCR array, supported the hypothesis that integrin αvβ8 inhibition alters hepatocyte TGFβ signaling towards a pro-regenerative phenotype. A diethylnitrosamine-induced model of hepatocellular carcinoma, employed to examine the possibility that this pro-proliferative phenotype might be oncogenic, revealed no difference in either tumor number or size...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research