| http://purl.uniprot.org/citations/35385340 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35385340 | http://www.w3.org/2000/01/rdf-schema#comment | "Diabetic neuropathic pain (DNP) is a common and devastating complication in patients with diabetes. The mechanisms mediating DNP are not completely elucidated, and effective treatments are lacking. A-fiber sensory neurons have been shown to mediate the development of mechanical allodynia in neuropathic pain, yet the molecular basis underlying the contribution of A-fiber neurons is still unclear. Here, we report that the orphan G protein-coupled receptor 177 (GPR177) in A-fiber neurons drives DNP via WNT5a-mediated activation of transient receptor potential vanilloid receptor-1 (TRPV1) ion channel. GPR177 is mainly expressed in large-diameter A-fiber dorsal root ganglion (DRG) neurons and required for the development of DNP in mice. Mechanistically, we found that GPR177 mediated the secretion of WNT5a from A-fiber DRG neurons into cerebrospinal fluid (CSF), which was necessary for the maintenance of DNP. Extracellular perfusion of WNT5a induced rapid currents in both TRPV1-expressing heterologous cells and nociceptive DRG neurons. Computer simulations revealed that WNT5a has the potential to bind the residues at the extracellular S5-S6 loop of TRPV1. Using a peptide able to disrupt the predicted WNT5a/TRPV1 interaction suppressed DNP- and WNT5a-induced neuropathic pain symptoms in rodents. We confirmed GPR177/WNT5A coexpression in human DRG neurons and WNT5A secretion in CSF from patients with DNP. Thus, our results reveal a role for WNT5a as an endogenous and potent TRPV1 agonist, and the GPR177-WNT5a-TRPV1 axis as a driver of DNP pathogenesis in rodents. Our findings identified a potential analgesic target that might relieve neuropathic pain in patients with diabetes."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.org/dc/terms/identifier | "doi:10.1126/scitranslmed.abh2557"xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Guo R."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Liu S."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Duan S."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Luo H."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Wu H."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Shen C."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Yang F."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Ma Q."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Han Q."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Zhang S.X."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Chen X.Y."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Xu Z.Z."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Chen W.B."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Xie Y.K."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Tian J.L."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Qiu X.Y."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/author | "Zhen X.H."xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/name | "Sci Transl Med"xsd:string |
| http://purl.uniprot.org/citations/35385340 | http://purl.uniprot.org/core/pages | "eabh2557"xsd:string |