Alpha-syntrophin deficiency protects against non-alcoholic steatohepatitis associated increase of macrophages, CD8+ T-cells and galectin-3 in the liver.

Alpha-syntrophin deficiency protects against non-alcoholic steatohepatitis associated increase of macrophages, CD8+ T-cells and galectin-3 in the liver. Exp Mol Pathol. 2019 Dec 24;:104363 Authors: Rein-Fischboeck L, Haberl EM, Bajraktari G, Feder S, Pohl R, Eggenhofer E, Buechler C Abstract Non-alcoholic steatohepatitis (NASH) is characterized by immune cell infiltration. Loss of the scaffold protein alpha-syntrophin (SNTA) protected mice from hepatic inflammation in the methionine-choline-deficient (MCD) diet model. Here, we determined increased numbers of macrophages and CD8+ T-cells in MCD diet induced NASH liver of wild type mice. In the mutant animals these NASH associated changes in immune cell composition were less pronounced. Further, there were more γδ T-cells in the NASH liver of the null mice. Galectin-3 protein in the hepatic non-parenchymal cell fraction was strongly induced in MCD diet fed wild type but not mutant mice. Antioxidant enzymes declined in NASH liver with no differences between the genotypes. To identify the target cells responsive to SNTA loss in-vitro experiments were performed. In the human hepatic stellate cell line LX-2, SNTA did not regulate pro-fibrotic or antioxidant proteins like alpha-smooth muscle actin or catalase. Soluble galectin-3 was, however, reduced upon SNTA knock-down and increased upon SNTA overexpression. SNTA deficiency neither affected cell proliferation nor cell death of LX-2 cell...
Source: Experimental and Molecular Pathology - Category: Pathology Authors: Tags: Exp Mol Pathol Source Type: research