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Alpha-syntrophin deficiency protects against non-alcoholic steatohepatitis associated increase of macrophages, CD8+ T-cells and galectin-3 in the liver.
Rein-Fischboeck, Lisa; Haberl, Elisabeth M; Bajraktari, Ganimete; Feder, Susanne; Pohl, Rebekka; Eggenhofer, Elke; Buechler, Christa.
Afiliação
  • Rein-Fischboeck L; Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
  • Haberl EM; Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
  • Bajraktari G; Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
  • Feder S; Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
  • Pohl R; Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
  • Eggenhofer E; Department of Surgery, Experimental Surgery, Regensburg University Hospital, Regensburg, Germany.
  • Buechler C; Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany. Electronic address: christa.buechler@klinik.uni-regensburg.de.
Exp Mol Pathol ; 113: 104363, 2020 04.
Article em En | MEDLINE | ID: mdl-31881201
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 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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Proteínas de Ligação ao Cálcio / Linfócitos T CD8-Positivos / Galectina 3 / Hepatopatia Gordurosa não Alcoólica / Fígado / Macrófagos / Proteínas de Membrana / Proteínas Musculares Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Revista: Exp Mol Pathol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Proteínas de Ligação ao Cálcio / Linfócitos T CD8-Positivos / Galectina 3 / Hepatopatia Gordurosa não Alcoólica / Fígado / Macrófagos / Proteínas de Membrana / Proteínas Musculares Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Revista: Exp Mol Pathol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Alemanha