Journal article
GPR126 Protein Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Receptor Signaling
The Journal of biological chemistry, Vol.289(50), pp.34871-34885
12/12/2014
DOI: 10.1074/jbc.M114.571000
PMCID: PMC4263886
PMID: 25217645
Abstract
Background: GPR126 plays critical roles in development, but its function in vessels is not well characterized. Results: GPR126 regulates angiogenesis by modulating endothelial cell proliferation and migration via regulation of Vegfr2 expression. Conclusion: GPR126 is important for physiological and pathological angiogenesis. Significance: This finding provides a new functional mechanism for the regulation of angiogenesis.
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.
Details
- Title: Subtitle
- GPR126 Protein Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Receptor Signaling
- Creators
- Hengxiang Cui - East China Normal UniversityYeqi Wang - Yale UniversityHuizhe Huang - Chongqing Medical UniversityWenjie Yu - East China Normal UniversityMin Bai - Hainan Medical UniversityLong Zhang - East China Normal UniversityBrad A. Bryan - Texas Tech University Health Sciences CenterYuan Wang - East China Normal UniversityJian Luo - East China Normal UniversityDali Li - East China Normal UniversityYanlin Ma - Hainan Medical UniversityMingyao Liu - East China Normal University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.289(50), pp.34871-34885
- DOI
- 10.1074/jbc.M114.571000
- PMID
- 25217645
- PMCID
- PMC4263886
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 15
- Grant note
- R15HL098931 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 14140900300 / Science and Technology Commission of Shanghai Municipality; Science & Technology Commission of Shanghai Municipality (STCSM) R15HL098931 / National Institutes of Health from NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 2012CB910400; 2010CB945403 / State Key Development Programs of China 30800627; 30930055; 31171318 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 12/12/2014
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984746240302771
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