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Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Cell+Mol+Med 2017 ; 21 (11): 2963-73 Nephropedia Template TP
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MiR?122 modification enhances the therapeutic efficacy of adipose tissue?derived mesenchymal stem cells against liver fibrosis #MMPMID28544786
Lou G; Yang Y; Liu F; Ye B; Chen Z; Zheng M; Liu Y
J Cell Mol Med 2017[Nov]; 21 (11): 2963-73 PMID28544786show ga
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR?122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR?122 modification can improve the therapeutic efficacy of adipose tissue?derived MSCs in treating liver fibrosis. MiR?122?modified AMSCs (AMSC?122) were constructed through lentivirus?mediated transfer of pre?miR?122. MiR?122?modified AMSCs expressed high level of miR?122, while they retained their phenotype and differentiation potential as naïve AMSCs. AMSC?122 more effectively suppressed the proliferation of and collagen maturation in HSCs than scramble miRNA?modified AMSCs. In addition, AMSC?derived exosomes mediated the miR?122 communication between AMSCs and HSCs, further affecting the expression levels of miR?122 target genes, such as insulin?like growth factor receptor 1 (IGF1R), Cyclin G(1) (CCNG1) and prolyl?4?hydroxylase ?1 (P4HA1), which are involved in proliferation of and collagen maturation in HSCs. Moreover, miR?122 modification enhanced the therapeutic efficacy of AMSCs in the treatment of carbon tetrachloride (CCl4)?induced liver fibrosis by suppressing the activation of HSCs and alleviating collagen deposition. Results demonstrate that miR?122 modification improves the therapeutic efficacy of AMSCs through exosome?mediated miR?122 communication; thus, miR?122 modification is a new potential strategy for treatment of liver fibrosis.