Anti-TGF beta-1 receptor inhibitor mediates the efficacy of the human umbilical cord mesenchymal stem cells against liver fibrosis through TGF beta-1/Smad pathway

摘要

The aim of the current investigation was to evaluate the anti-fibrosis potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further to explore some of its underlying mechanisms. Hepatic fibrosis mice model was induced by CCl4. Liver function parameters in serum and fibrosis-associated markers in tissues were detected. Moreover, SB-431542, an anti-TGF beta-1 receptor inhibitor, was employed in vitro to reveal the underlying mechanism of TGF beta-1/Smad pathway on hUC-MSCs against liver fibrosis. In the present study, we illustrated that hUC-MSCs could differentiate into osteogenic, adipogenic, and cartilage. Liver fibrosis was attenuated with hUC-MSCs treatment, determined by reductions of AST, ALT. and fibrosis area, along with some critical parameters including TGF beta-1, alpha-SMA, and TIMP-1. However, TGF beta-1 receptor antagonist SB-431542 reduced the paracrine TGF beta-1 expression of hUC-MSCs and blunted the activation of downstream target genes. Furthermore, the restrained hUC-MSCs proliferation and migration induced by SB-431542 could be reversed by si-TGF beta-1. These results demonstrated that TGF beta-1 receptor inhibitor improved the repair potential of hUC-MSCs against hepatic injury through TGF beta-1/Smad pathway, which contributed to improving the therapeutic efficiency of liver fibrosis.