title: Pim protein kinase-3 is regulated by TNF-α and promotes endothelial cell sprouting.
abstract: Tumor necrosis factor-α (TNF-α) 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-α transiently increased Pim-3 mRNA expression, and this was mediated through Tumor necrosis factor-α receptor-1 (TNFR1) pathway in ECs. TNF-α could promote stabilization of Pim- 3 mRNA in ECs. Small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired TNF-α-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-α-induced angiogenesis.
authors.affiliation: Department of Cardiovascular Diseases, Renmin Hospital of Wuhan University, Wuhan City, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Yang
authors.forename: Yinfang
authors.initials: Y
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Qian
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; C059485:matrigel; D003094:Collagen; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases