PMID- 28181132 OWN - NLM STAT- MEDLINE DCOM- 20170512 LR - 20181113 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 429 IP - 1-2 DP - 2017 May TI - Anti-TGFbeta-1 receptor inhibitor mediates the efficacy of the human umbilical cord mesenchymal stem cells against liver fibrosis through TGFbeta-1/Smad pathway. PG - 113-122 LID - 10.1007/s11010-017-2940-1 [doi] AB - 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 CCl(4). Liver function parameters in serum and fibrosis-associated markers in tissues were detected. Moreover, SB-431542, an anti-TGFbeta-1 receptor inhibitor, was employed in vitro to reveal the underlying mechanism of TGFbeta-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 TGFbeta-1, alpha-SMA, and TIMP-1. However, TGFbeta-1 receptor antagonist SB-431542 reduced the paracrine TGFbeta-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-TGFbeta-1. These results demonstrated that TGFbeta-1 receptor inhibitor improved the repair potential of hUC-MSCs against hepatic injury through TGFbeta-1/Smad pathway, which contributed to improving the therapeutic efficiency of liver fibrosis. FAU - Xuan, Ji AU - Xuan J AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - Feng, Wang AU - Feng W AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - An, Zheng-Tao AU - An ZT AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - Yang, Jian AU - Yang J AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - Xu, Hua-Bing AU - Xu HB AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - Li, Jing AU - Li J AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - Zhao, Zhi-Fei AU - Zhao ZF AD - Bayi Hospital Affiliated Nanjing University of Chinese Medicine, No. 34 Yang Gong Jing 34 District, Nanjing, 210002, People's Republic of China. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. FAU - Wen, Wei AU - Wen W AD - 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. AD - Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China. wenweiabc@yeah.net. AD - Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210000, Jiangsu, People's Republic of China. wenweiabc@yeah.net. LA - eng PT - Journal Article DEP - 20170208 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide) RN - 0 (Benzamides) RN - 0 (Dioxoles) RN - 0 (Smad Proteins) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Animals MH - Benzamides/*pharmacology MH - Carbon Tetrachloride/toxicity MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Combined Modality Therapy MH - Dioxoles/*pharmacology MH - Disease Models, Animal MH - Gene Expression Regulation/drug effects MH - Humans MH - Liver Cirrhosis/chemically induced/metabolism/*therapy MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mice MH - Signal Transduction/drug effects MH - Smad Proteins/*metabolism MH - Transforming Growth Factor beta1/*metabolism MH - Treatment Outcome MH - Umbilical Cord/*cytology OTO - NOTNLM OT - Human umbilical cord mesenchymal stem cells OT - Liver fibrosis OT - TGFbeta-1/Smad pathway OT - Transforming growth factor-beta1 EDAT- 2017/02/10 06:00 MHDA- 2017/05/13 06:00 CRDT- 2017/02/10 06:00 PHST- 2016/11/16 00:00 [received] PHST- 2017/01/16 00:00 [accepted] PHST- 2017/02/10 06:00 [pubmed] PHST- 2017/05/13 06:00 [medline] PHST- 2017/02/10 06:00 [entrez] AID - 10.1007/s11010-017-2940-1 [pii] AID - 10.1007/s11010-017-2940-1 [doi] PST - ppublish SO - Mol Cell Biochem. 2017 May;429(1-2):113-122. doi: 10.1007/s11010-017-2940-1. Epub 2017 Feb 8.