Journal
CLINICAL AND EXPERIMENTAL NEPHROLOGY
Volume 17, Issue 1, Pages 32-40Publisher
SPRINGER
DOI: 10.1007/s10157-012-0670-y
Keywords
Hydrogen sulfide (H2S); Cystathionine beta-synthase (CBS); Cystathionine gamma-lyase (CSE); Diabetic nephropathy
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Funding
- Aichi Diabetes Rheumatoid Gout Foundation
- KAKENHI from Japan Society Promotion of Science [21591146, 22790255]
- Oita University
- Ministry of Health, Labor and Welfare of Japan
- Oita Broadcasting System Cultural Foundation
- Oita University Venture Business Laboratory
- Grants-in-Aid for Scientific Research [21591146, 23791039, 22790255, 22590886] Funding Source: KAKEN
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Hydrogen sulfide (H2S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries. Cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H2S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. The present study examined the localization of both enzymes in the normal kidney and the effect of the H2S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic beta-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H2S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H2S production. H2S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.
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