Ask about this productRelated genes to: GPR75 antibody
- Gene:
- GPR75 NIH gene
- Name:
- G protein-coupled receptor 75
- Previous symbol:
- -
- Synonyms:
- WI-31133
- Chromosome:
- 2p16.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-22
- Date modifiied:
- 2016-10-05
Related products to: GPR75 antibody
Related articles to: GPR75 antibody
- Diabetes mellitus (diabetes) is a major health burden with the highest mortality rate, affecting an estimated 537 million adults worldwide. The treatment of diabetes remains complex owing to insulin resistance, β-cell dysfunction, metabolic inflammation, and progressive organ damage. While G-protein-coupled receptors (GPCRs) selectively suppress many pathological diseases, the functional characteristics of orphan GPCRs (oGPCRs) remain unexplored as therapeutic targets for diabetes. This review comprehensively evaluates oGPCRs and their roles in diabetes. Orphan receptors are classified based on their functional groups: i) insulin secretagogues such as GPR119 and GPR142, ii) transcriptional and regulatory modulators such as GPR27, and iii) metabolic sensors such as GPR75 and GPR91. We further explored the biological roles of these receptors in the pancreas, adipose tissue, liver, and kidneys. In addition, we mapped the convergence of oGPCR signaling with the pharmacological properties of FDA-approved antidiabetic therapies. The major roles of incretin signaling, AMPK-mediated energy sensing, insulin secretion pathways, inflammatory signaling networks, and sodium-glucose cotransporter 2 (SGLT2) -associated organ protection are addressed. We also report the functionality of these receptors on a receptor-by-receptor basis and prioritize them based on biological relevance, druggability, and translational feasibility. Furthermore, potential repurposable drugs targeting oGPCR pathways, along with existing nondiabetic medications, are highlighted. Finally, we discuss how emerging technologies, including single-cell RNA sequencing, spatial transcriptomics, and artificial intelligence- and structure-based drug design, accelerate GPCR deorphanization and therapeutic development. Overall, this report highlights the significant role of oGPCRs as therapeutic targets and drug repurposing opportunities for developing precision medicine and emphasizes the need for further research on oGPCR signaling in the treatment of diabetes. - Source: PubMed
Publication date: 2026/08/19
Chandrabose SurekaMuniyandi VikramanGeddawy AymanThiyagarajan RameshMurugesan AkshayaKandhavelu Meenakshisundaram - Hyperuricemia-related vascular endothelial injury is closely associated with hypertension, atherosclerosis, and other cardiovascular diseases. Although GPR75 has been implicated in vascular inflammation and hypertension, whether it mediates hyperuricemia-induced endothelial dysfunction and how it is regulated upstream remain unknown. - Source: PubMed
Publication date: 2026/08/07
Fu JiawuHe JunbingLi KeshenZhang MantingLi JiekaiLiu YuchunChen YusenBi Wei - Bronchopulmonary dysplasia (BPD), a debilitating chronic respiratory condition afflicting preterm neonates, stems from oxidative injury and is characterized by arrested alveolar growth and aberrant inflammatory responses. This investigation uncovers a novel mechanistic axis in which the 20-hydroxyeicosatetraenoic acid (20-HETE)/GPR75 signaling cascade acts as a previously unrecognized driver of NLRP1 inflammasome activation in neonatal BPD, thereby linking oxidative stress to inflammatory signaling via p53. Using murine hyperoxia models, we observe that excessive oxygen exposure selectively upregulates GPR75 expression and 20-HETE biosynthesis within alveolar epithelial cells. Genetic inactivation of Gpr75 in vivo significantly attenuated hyperoxia-induced lung injury, oxidative stress, and NLRP1-dependent secretion of interleukin-1β and interleukin-18. Mechanistic dissection revealed that 20-HETE induces NLRP1 inflammasome assembly in rat alveolar epithelia via p53-mediated signaling. In vitro corroboration via lentiviral-mediated Gpr75 silencing, with scrambled shRNA serving as a negative control, further validated its role in hyperoxia-triggered NLRP1 activation and cytokine release (P < 0.01 vs. scrambled control). Collectively, these findings establish the 20-HETE/GPR75 axis as a critical regulator of inflammasome-dependent pathogenesis in BPD. Blockade of this axis inhibits inflammasome assembly and downstream inflammation by suppressing p53 signaling. These results highlight this axis as a promising therapeutic target to mitigate oxygen-induced injury and inflammatory sequelae in preterm infants. - Source: PubMed
Xu QiuXiangTian XiaoLiLi BinKang Jian - Mitochondrial dysfunction plays a crucial role in retinal ganglion cells (RGCs) injury, the early pathogenesis of diabetic retinopathy (DR). G protein-coupled receptor 75 (GPR75), an orphan receptor, is a novel regulator of metabolic diseases. However, the role and mechanisms of GPR75 underlying diabetic RGCs mitochondrial dysfunction have not been reported. To investigate the function of GPR75, we knockdown the receptor in streptozotocin (STZ) mice and high glucose (HG)-treated primary RGCs. Our investigations revealed an upregulation of GPR75 in DR. Furthermore, we demonstrated that GPR75 knockdown could mitigate the progression of DR, with its protective effects associated with the inhibition of mitochondrial dysfunction in RGCs. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a regulator of mitochondrial function and a cellular energy sensor, was identified as a novel target of GPR75. Immunofluorescence and co-immunoprecipitation (CO-IP) analyses confirmed the co-localization and interaction between GPR75 and AMPK in RGCs. Mechanistically, the upregulation of GPR75 inhibits AMPK-mediated mitochondrial homeostasis, resulting in impaired mitochondrial dynamics, disrupted energy metabolism, and elevated reactive oxygen species (ROS), which ultimately trigger pyroptosis and apoptosis in RGCs. Notably, the AMPK-activator AICAR mitigates GPR75-induced mitochondrial dysfunction, pyroptosis, and apoptosis. In summary, our findings suggest that the targeted inhibition of GPR75 may represent a promising therapeutic strategy for DR. - Source: PubMed
Publication date: 2026/07/15
Liu MengrenCheng XueLiu WenqiangYu HongDanYu ShengxueWang YaliChen XinyuanMiao QuanlingYuan YirongDai WeiHu JiaweiZhang NaSui JiahengLiu XuezhengZuo Zhongfu - G-protein-coupled receptor 75 (GPR75) has emerged as an important mediator in diet-induced obesity (DIO) and a promising therapeutic target for anti-obesity drugs. However, the anatomical location of GPR75 in the brain remains unclear, hindering the understanding of GPR75 biology in DIO. Here, we generated a new GPR75-GFP-Ires-Cre knockin mouse strain, in which the Cre expression is driven by the endogenous GPR75 promoter and the GFP is fused with the C-terminal of the GPR75 protein. Both Cre and GFP were confirmed to be colocalized with the endogenous GPR75 expression. In addition, the GPR75-GFP fusion protein remains functionally normal with unaltered susceptibility to DIO. Moreover, using this mouse strain, we found that GPR75 is broadly expressed throughout the brain and mainly localized to the cytoplasm of brain neurons. This new genetic tool can therefore be used to study the neural basis for GPR75 in mediating DIO. - Source: PubMed
Publication date: 2026/06/02
Wheeler Emma CYang RunzhouFarmer Stephen MZhang ShengZhang NingyanAn ZhiqiangTong Qingchun