PMID- 25613158 OWN - NLM STAT- MEDLINE DCOM- 20151013 LR - 20211103 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 35 IP - 2 DP - 2015 TI - Mesenchymal stem cells mitigate cirrhosis through BMP7. PG - 433-40 LID - 10.1159/000369708 [doi] AB - BACKGROUND/AIMS: Transplantation of mesenchymal stem cells (MSCs) has therapeutic effects on various diseases, while its effect on developing cirrhosis as well as the underlying mechanism remained largely unknown. METHODS: Twenty C57BL/6 mice were randomly separated into 2 groups of ten each. One group received transplantation of MSCs, while the other group received saline as control. The mice then received intraperitoneal injection of carbon tetrachloride (CCl4) twice per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure, sodium balance and excretion. Transcripts of transforming growth factor beta 1 (TGFbeta1) and bone morphogenic protein 7 (BMP7) in the mouse livers were quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this model, and compared to MSCs. RESULTS: Liver fibrosis, portal hypertension and sodium retention that were developed by CCl4, were all significantly alleviated by MSCs transplantation, which decreased TGFbeta1 levels and increased BMP7 levels in the injured liver. MSCs were found to express extremely high levels of BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of MSCs against CCl4-induced cirrhosis. CONCLUSIONS: MSCs mitigate cirrhosis through their production of BMP7 against the fibrogenic effect of TGFbeta1 in the injured liver. CI - (c) 2015 S. Karger AG, Basel. FAU - Li, Bing AU - Li B AD - Liver Fibrosis Diagnosis and Treatment Center, 302 Hospital of PLA, Beijing, China. FAU - Shao, Qing AU - Shao Q FAU - Ji, Dong AU - Ji D FAU - Li, Fan AU - Li F FAU - Chen, Guofeng AU - Chen G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150115 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Bone Morphogenetic Protein 7) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - 0 (bmp7 protein, mouse) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Animals MH - Bone Morphogenetic Protein 7/antagonists & inhibitors/*genetics MH - Carbon Tetrachloride MH - Cells, Cultured MH - Gene Expression Regulation MH - Gene Knockdown Techniques MH - Hypertension, Portal/pathology/*therapy MH - Liver Cirrhosis, Experimental/chemically induced/genetics/pathology/*therapy MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Random Allocation MH - Transforming Growth Factor beta1/*genetics EDAT- 2015/01/24 06:00 MHDA- 2015/10/16 06:00 CRDT- 2015/01/24 06:00 PHST- 2014/11/27 00:00 [accepted] PHST- 2015/01/24 06:00 [entrez] PHST- 2015/01/24 06:00 [pubmed] PHST- 2015/10/16 06:00 [medline] AID - 000369708 [pii] AID - 10.1159/000369708 [doi] PST - ppublish SO - Cell Physiol Biochem. 2015;35(2):433-40. doi: 10.1159/000369708. Epub 2015 Jan 15.