Rein-Fischboeck, Lisa and Haberl, Elisabeth M. and Bajraktari, Ganimete and Feder, Susanne and Pohl, Rebekka and Eggenhofer, Elke and Buechler, Christa (2020) Alpha-syntrophin deficiency protects against non-alcoholic steatohepatitis associated increase of macrophages, CD8(+) T-cells and galectin-3 in the liver. EXPERIMENTAL AND MOLECULAR PATHOLOGY, 113: 104363. ISSN 0014-4800, 1096-0945
Full text not available from this repository. (Request a copy)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 gamma delta 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 cells. In the macrophage cell line RAW264.7 low SNTA indeed caused higher galectin-3 production whereas release of TNF and cell viability were normal. Moreover, SNTA had no effect on hepatocyte chemerin and CCL2 expression. Overall, SNTA loss improved NASH without causing major effects in macrophage, hepatocyte and hepatic stellate cell lines. SNTA null mice fed the MCD diet had less body weight loss and this seems to contribute to improved liver health of the mutant mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STELLATE CELLS; OXIDATIVE STRESS; ADIPOSE-TISSUE; INFLAMMATION; PROMOTES; MODEL; MICE; ADIPONECTIN; RECRUITMENT; ACTIVATION; RAW264.7; Lymphocytes; CCL2; Proliferation; LX-2 cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 06:32 |
| Last Modified: | 29 Mar 2021 06:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44841 |
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