PMID- 20533298 OWN - NLM STAT- MEDLINE DCOM- 20110125 LR - 20181201 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 111 IP - 2 DP - 2010 Oct 1 TI - Mechanism of TNF-alpha-induced migration and hepatocyte growth factor production in human mesenchymal stem cells. PG - 469-75 LID - 10.1002/jcb.22729 [doi] AB - Accumulating evidence suggests that mesenchymal stem cells (MSCs) may decrease destructive inflammation and reduce tissue loss. Tumor necrosis factor-alpha (TNF-alpha) plays a central role in induction of proinflammatory signaling and paradoxically activates intracellular anti-inflammatory survival pathways. In this study, we investigated whether TNF-alpha could induce a chemotactic effect on human MSCs and stimulate their production of anti-inflammatory factors in vitro, as well as determined mechanisms that mediated this effect. Migration assays demonstrated that TNF-alpha had a chemotactic effect on MSCs. TNF-alpha increased both hepatocyte growth factor (HGF) mRNA expression in MSCs and HGF secretion in conditioned medium. These effects were dependent on the p38 MAPK and PI3K/Akt, but not JNK and ERK signaling pathways. Furthermore, these effects were inhibited by a specific neutralizing antibody to TNF receptor II, but not TNF receptor I. We conclude that TNF-alpha can enhance human MSCs migration and stimulate their production of HGF. These effects are mediated via a specific TNF receptor and signaling pathways. CI - (c) 2010 Wiley-Liss, Inc. FAU - Zhang, Aibin AU - Zhang A AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. FAU - Wang, Yan AU - Wang Y FAU - Ye, Zhou AU - Ye Z FAU - Xie, Haiyang AU - Xie H FAU - Zhou, Lin AU - Zhou L FAU - Zheng, Shusen AU - Zheng S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Culture Media, Conditioned) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Cell Movement/drug effects MH - Cells, Cultured MH - Culture Media, Conditioned MH - Hepatocyte Growth Factor/*biosynthesis MH - Humans MH - Mesenchymal Stem Cells MH - RNA, Messenger/analysis MH - Receptors, Tumor Necrosis Factor MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2010/06/10 06:00 MHDA- 2011/01/28 06:00 CRDT- 2010/06/10 06:00 PHST- 2010/06/10 06:00 [entrez] PHST- 2010/06/10 06:00 [pubmed] PHST- 2011/01/28 06:00 [medline] AID - 10.1002/jcb.22729 [doi] PST - ppublish SO - J Cell Biochem. 2010 Oct 1;111(2):469-75. doi: 10.1002/jcb.22729.