G Protein–Coupled Receptor 35 Suppresses Oxidative Stress Responsive Kinase 1 in Diabetic Wound Healing
Endothelial cell dysfunction is a crucial feature of diabetic wound healing. The underlying molecular mechanisms are poorly understood. We investigated how G protein-coupled receptor 35 (GPR35) inhibition accelerates diabetic wound healing. We found that GPR35 modulated endothelial cell behavior in vitro and identified oxidative stress responsive 1 as its target. Inhibiting GPR35 rescued the healing process in animals with hyperglycemia. This study uncovers novel molecular mechanisms underlying the benefit of GPR35 inhibition on endothelial cell angiogenesis and provides proof-of-concept evidence for therapeutic strategies targeting GPR35 in the endothelium as a potential therapy for diabetic wound care.
Authors
- Sai Pranathi Meda Venkata (ORCID: https://orcid.org/0000-0002-1771-4806)
- Graeme Milligan (ORCID: https://orcid.org/0000-0002-6946-3519)
- Jie‐Mei Wang (ORCID: https://orcid.org/0000-0002-8723-4410)
- Liping Xu (ORCID: https://orcid.org/0000-0003-3370-2386)
- Morgan Minjares (ORCID: https://orcid.org/0000-0001-9523-0703)
- Anjaneyulu Kowluru (ORCID: https://orcid.org/0000-0003-1700-0077)
- Jan Hendrik Niess
- Hainan Li
- Hassan Melhem
Institutions
- Eugene Applebaum College of Pharmacy and Health Sciences (US)
- University of Basel (CH)
- Wayne State University (US)
- University Hospital of Basel (CH)
- John D. Dingell VA Medical Center (US)
- The Barbara Ann Karmanos Cancer Institute (US)
- University of Glasgow (GB)
Publication Details
- Journal
- Diabetes
- Published
- 2025-04-23
- DOI
- https://doi.org/10.2337/db24-0737
- Primary Topic
- Angiogenesis and VEGF in Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00