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Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis #MMPMID28115038
Jang YJ; An SY; Kim JH
BMB Rep 2017[]; 50 (2): 58-9 PMID28115038show ga
The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the TGF?/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated TGF? type I receptor expression by binding to ?v?3 integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating TGF?-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.