BACKGROUND: Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear. AIMS: The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs. METHODS: After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs. RESULTS: BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation. CONCLUSIONS: Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs.
BACKGROUND:Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear. AIMS: The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs. METHODS: After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant ratadrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs. RESULTS: BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation. CONCLUSIONS: Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs.
Authors: Daniel Ferracioli Brandão; Leandra Naira Zambelli Ramalho; Fernando Silva Ramalho; Sérgio Zucoloto; Ana de Lourdes Candolo Martinelli; Orlando de Castro e Silva Journal: Acta Cir Bras Date: 2006 Impact factor: 1.388
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