MrgD deficiency in male mice led to marked proteinuria and significant tubulointerstitial injury and fibrosis, indicating its crucial role in renal health.
Does MrgD deficiency affect renal structure and function in male mice?
Basal MrgD deficiency promotes tubular dysfunction, injury, and fibrosis, highlighting a protective role for this novel Renin-Angiotensin System axis in kidney physiology.
Kidney diseases are non-communicable, progressive diseases with high morbidity and mortality rates worldwide. A key feature of disease progression is the development of tubulointerstitial injury accompanied by proteinuria, a process mediated in part by dysregulation of the Renin-Angiotensin System (RAS). Recently, a novel protective RAS axis consisting of alamandine (Ala) and its receptor, the Mas-related G protein-coupled receptor type D (MrgD), has been identified. While the Ala/MrgD pathway has been implicated in the cardiovascular regulation, its role in renal physiology remains unknown. In this study, we investigated whether basal MrgD deficiency affects the renal structure and function. Male 8-12-week-old C57Bl6/J wild-type (WT) and MrgD knockout (MrgD-KO) mice were used. MrgD-KO exhibited reduced water intake and urine output, increased tubular reabsorption of Na+ and glucose, and marked proteinuria associated with increased fractional excretion of proteins. In addition, MrgD deficiency was associated with elevated urinary lactate dehydrogenase levels, increased urinary proteins: creatinine ratio, enhanced urinary γ-glutamyltransferase activity, and the presence of tubulointerstitial injury and fibrosis in the renal cortex. Collectively, these findings demonstrate that basal MrgD deficiency promotes tubular dysfunction and injury, thereby expanding current understanding of the role of novel RAS peptides in kidney disease.
OLIVEIRA et al. (2026) studied this question. MrgD deficiency in male mice led to marked proteinuria and significant tubulointerstitial injury and fibrosis, indicating its crucial role in renal health.
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