Anti-TGFβ-1 receptor inhibitor mediates the efficacy of the human umbilical cord mesenchymal stem cells against liver fibrosis through TGFβ-1/Smad pathway.
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-TGFβ-1 receptor inhibitor, was employed in vitro to reveal the underlying mechanism of TGFβ-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 TGFβ-1, α-SMA, and TIMP-1. However, TGFβ-1 receptor antagonist SB-431542 reduced the paracrine TGFβ-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-TGFβ-1. These results demonstrated that TGFβ-1 receptor inhibitor improved the repair potential of hUC-MSCs against hepatic injury through TGFβ-1/Smad pathway, which contributed to improving the therapeutic efficiency of liver fibrosis.
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Ji
J
Xuan
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Wang
W
Feng
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Zheng-Tao
ZT
An
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Jian
J
Yang
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Hua-Bing
HB
Xu
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Jing
J
Li
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China.
Zhi-Fei
ZF
Zhao
Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. wenweiabc@yeah.net.|Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. wenweiabc@yeah.net.|Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. wenweiabc@yeah.net.
Wei
W
Wen
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004149:Dioxoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D016896:Treatment Outcome; D014470:Umbilical Cord / Q000166:cytology*
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D051785:Smad Proteins; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride
Human umbilical cord mesenchymal stem cells; Liver fibrosis; TGFβ-1/Smad pathway; Transforming growth factor-β1