This study is led by Dr. Haisheng Zhou (Department of Biochemistry and Molecular Biology, Anhui Medical University, China) and Dr. Guoling Zhou (Center for Computational Integrative Biology, Massachusetts General Hospital, USA). They have identified a crucial protein, G protein-coupled receptor 107 (GPR107), that plays a protective role in the kidneys of individuals with diabetic nephropathy (DN), a serious complication of diabetes. The findings, recently published in Molecular Biomedicine , offer new insights into the mechanisms behind DN and suggest GPR107 as a potential therapeutic target for this debilitating disease.
DN is a leading cause of kidney failure worldwide. A hallmark of DN is the thickening of the glomerular basement membrane (GBM), a critical filter in the kidney, due to the abnormal buildup of COL4. This study reveals that GPR107 is essential for maintaining the proper balance of COL4 in the kidney's filtering cells (podocytes).
Researchers identified GPR107 as a key regulator of COL4 levels in the kidney, finding that reduced GPR107 in diabetic kidneys contributes to harmful COL4 accumulation, causing GBM thickening and kidney damage. They discovered that GPR107 facilitates the internalization of angiotensin II receptor type 1 (AT1R) in podocytes through clathrin-mediated endocytosis. In diabetic kidneys, GPR107 loss impairs this internalization, leading to increased AT1R signaling, which triggers a cascade that promotes COL4 production and inhibits its breakdown.
Key findings from the study include:
These findings highlight the potential of GPR107 as a therapeutic target in diabetic nephropathy. Strategies aimed at restoring or enhancing GPR107 function in the kidney could represent a novel approach to preventing or mitigating the progression of this debilitating disease. This research provides a strong rationale for developing targeted therapies that specifically address GPR107 dysregulation in the diabetic kidney.
The research team is now focused on exploring potential drug candidates that can modulate GPR107 activity and further investigating the role of GPR107 in other aspects of kidney health.
Molecular Biomedicine
G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy
11-Feb-2025