title: KLF4 Promotes Angiogenesis by Activating VEGF Signaling in Human Retinal Microvascular Endothelial Cells.
abstract: The transcription factor Krüppel-like factor 4 (KLF4) has been implicated in regulating cell proliferation, migration and differentiation in a variety of human cells and is one of four factors required for the induction of pluripotent stem cell reprogramming. However, its role has not been addressed in ocular neovascular diseases. This study investigated the role of KLF4 in angiogenesis and underlying molecular mechanisms in human retinal microvascular endothelial cells (HRMECs). The functional role of KLF4 in HRMECs was determined following lentiviral vector mediated inducible expression and shRNA knockdown of KLF4. Inducible expression of KLF4 promotes cell proliferation, migration and tube formation. In contrast, silencing KLF4 inhibits cell proliferation, migration, tube formation and induces apoptosis in HRMECs. KLF4 promotes angiogenesis by transcriptionally activating VEGF expression, thus activating the VEGF signaling pathway in HRMECs.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Department of Laboratory Animal Center, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Chuanhe
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Sims
authors.affiliation: Department of Laboratory Animal Center, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Weiwang
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Pfeffer
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Junming
authors.initials: J
authors.lastname: Yue
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012160:Retina / Q000166:cytology; D012171:Retinal Vessels / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A