| http://purl.uniprot.org/citations/36574661 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36574661 | http://www.w3.org/2000/01/rdf-schema#comment | "Impaired endothelial cell (EC)-mediated angiogenesis contributes to critical limb ischemia in diabetic patients. The sonic hedgehog (SHH) pathway participates in angiogenesis but is repressed in hyperglycemia by obscure mechanisms. We investigated the orphan G protein-coupled receptor GPR39 on SHH pathway activation in ECs and ischemia-induced angiogenesis in animals with chronic hyperglycemia. Human aortic ECs from healthy and type 2 diabetic (T2D) donors were cultured in vitro. GPR39 mRNA expression was significantly elevated in T2D. The EC proliferation, migration, and tube formation were attenuated by adenovirus-mediated GPR39 overexpression (Ad-GPR39) or GPR39 agonist TC-G-1008 in vitro. The production of proangiogenic factors was reduced by Ad-GPR39. Conversely, human ECs transfected with GPR39 siRNA or the mouse aortic ECs isolated from GPR39 global knockout (GPR39KO) mice displayed enhanced migration and proliferation compared with their respective controls. GPR39 suppressed the basal and ligand-dependent activation of the SHH effector GLI1, leading to attenuated EC migration. Coimmunoprecipitation revealed that the GPR39 direct binding of the suppressor of fused (SUFU), the SHH pathway endogenous inhibitor, may achieve this. Furthermore, in ECs with GPR39 knockdown, the robust GLI1 activation and EC migration were abolished by SUFU overexpression. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, the GPR39KO mice demonstrated a faster pace of revascularization from hind limb ischemia and lower incidence of tissue necrosis than GPR39 wild-type (GPR39WT) counterparts. These findings have provided a conceptual framework for developing therapeutic tools that ablate or inhibit GPR39 for ischemic tissue repair under metabolic stress."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2208541120"xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Li C."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Li H."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Nguyen H."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Xu L."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Milligan G."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Wang J.M."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Koh J.Y."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Kowluru A."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Meda Venkata S.P."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/author | "Minjares M."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/pages | "e2208541120"xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/title | "Inhibition of GPR39 restores defects in endothelial cell-mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis."xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://purl.uniprot.org/core/volume | "120"xsd:string |
| http://purl.uniprot.org/citations/36574661 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36574661 |
| http://purl.uniprot.org/citations/36574661 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36574661 |
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| http://purl.uniprot.org/uniprot/#_A4FVA5-mappedCitation-36574661 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36574661 |