PMID- 21870113 OWN - NLM STAT- MEDLINE DCOM- 20120130 LR - 20240204 IS - 0219-1032 (Electronic) IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 32 IP - 3 DP - 2011 Sep TI - Pim protein kinase-3 is regulated by TNF-alpha and promotes endothelial cell sprouting. PG - 235-41 LID - 10.1007/s10059-011-1026-z [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in pathological angiogenesis associated with inflammatory response. Pim-3 kinase belonging to serine/threonine protein kinases is a potent suppressor of myc-induced apoptosis. We have recently demonstrated that Pim-3 plays an essential role in endothelial cell (EC) spreading and migration. In this study, we showed that TNF-alpha transiently increased Pim-3 mRNA expression, and this was mediated through Tumor necrosis factor-alpha receptor-1 (TNFR1) pathway in ECs. TNF-alpha could promote stabilization of Pim- 3 mRNA in ECs. Small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired TNF-alpha-induced formation of EC membrane protrusions in vitro. Furthermore, Pim-3 silencing inhibited EC sprouting in subcutaneous Matrigel in vivo. eNOS mRNA abundance was lower in Pim-3 siRNA transfected ECs compared with the control ECs. These observations suggest that Pim-3 plays a role in TNF-alpha-induced angiogenesis. FAU - Yang, Handong AU - Yang H AD - Department of Cardiovascular Diseases, Renmin Hospital of Wuhan University, Wuhan City, China. FAU - Wang, Yinfang AU - Wang Y FAU - Qian, Hang AU - Qian H FAU - Zhang, Peng AU - Zhang P FAU - Huang, Congxin AU - Huang C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110823 PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (Drug Combinations) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Tumor Necrosis Factor-alpha) RN - 119978-18-6 (matrigel) RN - 9007-34-5 (Collagen) RN - EC 1.14.13.39 (NOS3 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 2.7.11.1 (PIM3 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Blotting, Western MH - Cell Movement MH - Cells, Cultured MH - Collagen/chemistry/metabolism MH - Drug Combinations MH - Female MH - Gene Expression MH - Gene Silencing/drug effects MH - Human Umbilical Vein Endothelial Cells/cytology/*metabolism MH - Humans MH - Laminin/chemistry/metabolism MH - Neoplasms/*blood supply/pathology MH - Neovascularization, Pathologic/genetics/*metabolism MH - Nitric Oxide Synthase Type III/genetics/*metabolism MH - Protein Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism MH - Proteoglycans/chemistry/metabolism MH - Proto-Oncogene Proteins/antagonists & inhibitors/genetics/*metabolism MH - RNA Stability MH - RNA, Messenger/analysis/biosynthesis MH - RNA, Small Interfering/pharmacology MH - Receptors, Tumor Necrosis Factor, Type I/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/genetics/*metabolism MH - Up-Regulation PMC - PMC3887632 EDAT- 2011/08/27 06:00 MHDA- 2012/01/31 06:00 PMCR- 2012/09/30 CRDT- 2011/08/27 06:00 PHST- 2011/02/14 00:00 [received] PHST- 2011/06/29 00:00 [accepted] PHST- 2011/06/28 00:00 [revised] PHST- 2011/08/27 06:00 [entrez] PHST- 2011/08/27 06:00 [pubmed] PHST- 2012/01/31 06:00 [medline] PHST- 2012/09/30 00:00 [pmc-release] AID - S1016-8478(23)10950-2 [pii] AID - ksmcb-32-235 [pii] AID - 10.1007/s10059-011-1026-z [doi] PST - ppublish SO - Mol Cells. 2011 Sep;32(3):235-41. doi: 10.1007/s10059-011-1026-z. Epub 2011 Aug 23.