Abstract
Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.
Highlights
Diabetic kidney injury is a leading cause of end-stage renal failure, predominantly due to the increase of diabetes and obesity [1,2]
We find that Hydrogen sulfide (H2 S) inhibits forskolin-induced renin degranulation in mast cells by lowering intracellular cyclic adenosine monophosphate (cAMP) level, protecting against isoproterenol (ISO)-induced heart failure [80]
The first evidence for the endothelial mesenchymal transition (EndMT) in renal fibrosis is established by Zeisberg and colleagues, their results demonstrate that a large proportion of myofibroblasts coexpress the endothelium marker CD31 in three mouse models, unilateral ureteral obstruction (UUO), genetic modification, STZ-induced diabetic nephropathy [135], suggesting that these fibroblasts are likely derived from endothelial cells and EndMT may substantially contribute to the development and progression of renal fibrosis
Summary
Diabetic kidney injury is a leading cause of end-stage renal failure, predominantly due to the increase of diabetes and obesity [1,2]. Most of cardiovascular disease mortality for diabetic patients is related to diabetic kidney disease [4]. Diabetic kidney disease is still a major contributor to morbidity and mortality of diabetic patients worldwide [5]. Molecules 2019, 24, 2857 of diabetic kidney disease are continuous, the current therapies only retard the disease progression but cannot cure it. Thereby, there is a pressing demand to identify novel therapies or targets for the treatment of diabetic kidney disease. We will discuss the recent experimental findings on the molecular mechanisms underlying the therapeutic effects of H2 S against diabetic kidney disease and its possibilities, challenges for clinical application in the future
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