Hydrogen Sulfide Regulates Homocysteine-Mediated Glomerulosclerosis

Background/Aims: In this study we tested the hypothesis that H2S regulates collagen deposition, matrix metalloproteinases (MMP) and inflammatory molecules during hyper-homocysteinemia (HHcy) resulting in attenuation of glomerulosclerosis and improved renal function. Materials and Methods: A genetic model of HHcy, cystathionine beta-synthase heterozygous (CBS+/-) and wild-type (WT) 2-kidney (2K) mice were used in this study and supplemented with or without NaHS (30 mu mol/l, H2S donor) in drinking water for 8 weeks. To expedite the renal damage associated with HHcy, uninephrectomized (1K) mice of similar groups were also used. Results: Results demonstrated that NAD(P) H oxidase (p47(phox) subunit) and blood pressure were upregulated in WT 1K, CBS+/-2K and CBS+/- 1K mice with downregulation of H2S production and reduced glomerular filtration rate. These changes were normalized with H2S supplementation. Both pro-and active MMP-2 and -9 and collagen protein expressions and glomerular depositions were also upregulated in WT 1K, CBS+/- 2K and CBS+/- 1K mice. Increased expressions of inflammatory molecules, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, as well as increased macrophage infiltration, were detected in WT 1K, CBS+/- 2K and CBS+/- 1K mice. These changes were ameliorated with H2S supplementation. Conclusion: Together, these results suggest that increased oxidative stress and decreased H2S in HHcy causes matrix remodeling and inflammation resulting in glomerulosclerosis and reduced renal function. Copyright (C) 2010 S. Karger AG, Basel