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Updated: Jun 13, 2026

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis
Utpal Sen1, Charu Munjal, Natia Qipshidze
1Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY 40202, USA. u0sen001 @ louisville.edu
Background/Aims:
In this study we tested the hypothesis that H(2)S regulates collagen deposition, matrix metalloproteinases (MMP) and inflammatory molecules during hyperhomocysteinemia (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 micromol/l, H(2)S 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 H(2)S production and reduced glomerular filtration rate. These changes were normalized with H(2)S 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 H(2)S supplementation.
Conclusion:
Together, these results suggest that increased oxidative stress and decreased H(2)S in HHcy causes matrix remodeling and inflammation resulting in glomerulosclerosis and reduced renal function.
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