title: GPR126 protein regulates developmental and pathological angiogenesis through modulation of VEGFR2 receptor signaling.
abstract: Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for development, wound healing, and tumor progression. The VEGF pathway plays irreplaceable roles during angiogenesis, but how other signals cross-talk with and modulate VEGF cascades is not clearly elucidated. Here, we identified that Gpr126, an endothelial cell-enriched gene, plays an important role in angiogenesis by regulating endothelial cell proliferation, migration, and tube formation. Knockdown of Gpr126 in the mouse retina resulted in the inhibition of hypoxia-induced angiogenesis. Interference of Gpr126 expression in zebrafish embryos led to defects in intersegmental vessel formation. Finally, we identified that GPR126 regulated the expression of VEGFR2 by targeting STAT5 and GATA2 through the cAMP-PKA-cAMP-response element-binding protein signaling pathway during angiogenesis. Our findings illustrate that GPR126 modulates both physiological and pathological angiogenesis through VEGF signaling, providing a potential target for the treatment of angiogenesis-related diseases.
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Hengxiang
authors.initials: H
authors.lastname: Cui
authors.affiliation: the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Yeqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: the Core Facility of Zebrafish Research, School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yu
authors.affiliation: the Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Reproductive Medical Center, Affiliated Hospital of Hainan Medical University, Haikou 570102, China.
authors.forename: Min
authors.initials: M
authors.lastname: Bai
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: the Center of Excellence in Cancer Research, Texas Tech University Health Sciences Center, El Paso, Texas 79905, and.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Bryan
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China, dlli@bio.ecnu.edu.cn.
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.affiliation: the Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Reproductive Medical Center, Affiliated Hospital of Hainan Medical University, Haikou 570102, China, mayl1990@foxmail.com.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China, the Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030 mlliu@bio.ecnu.edu.cn.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D047108:Embryonic Development; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D050989:GATA2 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology
chemical_list: C488660:ADGRG6 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C550767:Gpr126 protein, mouse; D043562:Receptors, G-Protein-Coupled; D050799:STAT5 Transcription Factor; D000242:Cyclic AMP; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Endothelial Cell; G Protein-coupled Receptor (GPCR); Protein Kinase A (PKA); VEGFR2; Vascular Endothelial Growth Factor (VEGF)