ArticleAmerican journal of physiology. Endocrinology and metabolism2013
Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 87 citations in OpenAlex.
- Article
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- Clinical Trial: Effects of Autologous Dendritic Cell Administration on Renal Hemodynamics and Inflammatory Biomarkers in Diabetic Kidney Disease.Diseases (Basel, Switzerland) · 2025Article
- Gut Microbiota and Their Metabolites: The Hidden Driver of Diabetic Nephropathy? Unveiling Gut Microbe's Role in DN.Journal of diabetes · 2025Review
- Article
- Protective Role of HDiabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Complex Pathophysiology of Acute Kidney Injury (AKI) in Aging: Epigenetic Regulation, Matrix Remodeling, and the Healing Effects of HBiomolecules · 2024Review
- Non-voltage-gated CaAmerican journal of physiology. Renal physiology · 2024Review
- Advances of Iron and Ferroptosis in Diabetic Kidney Disease.Kidney international reports · 2024Review
- Novel ray of hope for diabetic wound healing: Hydrogen sulfide and its releasing agents.Journal of advanced research · 2024Review
- Diabetic Nephropathy and Gaseous Modulators.Antioxidants (Basel, Switzerland) · 2023Review
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Glucosidase inhibitor, Nimbidiol ameliorates renal fibrosis and dysfunction in type-1 diabetes.Scientific reports · 2022Article
- The roles of hydrogen sulfide in renal physiology and disease states.Renal failure · 2022Review
- A Lack of GD3 Synthase Leads to Impaired Renal Expression of Connexins and Pannexin1 inInternational journal of molecular sciences · 2022Article
- GYY4137 Regulates Extracellular Matrix Turnover in the Diabetic Kidney by Modulating Retinoid X Receptor Signaling.Biomolecules · 2021Article
- Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy.International journal of molecular sciences · 2021Review
- Hydrogen Sulfide and the Kidney.Advances in experimental medicine and biology · 2021Article
- Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier.Frontiers in cell and developmental biology · 2021Article
- Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis.Antioxidants (Basel, Switzerland) · 2020Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Matrix metalloproteinase-9 (MMP-9) causes adverse remodeling, whereas hydrogen sulfide (H2S) rescues organs in vascular diseases. The involvement of MMP-9 and H2S in diabetic renovascular remodeling is, however, not well characterized. We determined whether MMP-9 regulates H2S generation and whether H2S modulates connexin through N-methyl-d-aspartate receptor (NMDA-R)-mediated pathway in the diabetic kidney. Wild-type (WT, C57BL/6J), diabetic (Akita, C57BL/6J-Ins2(Akita)), MMP-9(-/-) (M9KO), double knockout (DKO) of Akita/MMP-9(-/-) mice and in vitro cell culture were used in our study. Hyperglycemic Akita mice exhibited increased level of MMP-9 and decreased production of H2S. H2S-synthesizing enzymes cystathionine-β-synthase and cystathionine-γ-lyase were also diminished. In addition, increased expressions of NMDA-R1 and connexin-40 and -43 were observed in diabetic kidney. As expected, MMP-9 mRNA was not detected in M9KO kidneys. However, very thin protein expression and activity were detected. No other changes were noticed in M9KO kidney. In DKO mice, all the above molecules showed a trend toward baseline despite hyperglycemia. In vitro, glomerular endothelial cells treated with high glucose showed induction of MMP-9, attenuated H2S production, NMDA-R1 induction, and dysregulated conexin-40 and -43 expressions. Silencing MMP-9 by siRNA or inhibition of NMDA-R1 by MK801 or H2S treatment preserved connexin-40 and -43. We conclude that in diabetic renovascular remodeling MMP-9 plays a major role and that H2S has therapeutic potential to prevent adverse diabetic renal remodeling.
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