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Updated: May 10, 2026
08:32
Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
Low nitric oxide bioavailability upregulates renal heparin binding EGF-like growth factor expression
Tomoki Miyazawa1, Fenghua Zeng, Suwan Wang
1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Kidney International
|June 14, 2013
Summary
Decreased nitric oxide bioavailability elevates heparin-binding epidermal growth factor-like growth factor (HB-EGF) in diabetic kidney disease. This HB-EGF increase contributes to progressive diabetic nephropathy in mice lacking endothelial nitric oxide synthase (eNOS).
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Decreased nitric oxide (NO) bioavailability is implicated in diabetic nephropathy (DN) pathogenesis.
- The precise molecular mechanisms linking reduced NO to DN progression are not fully understood.
- Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potential mediator in kidney disease.
Purpose of the Study:
- To investigate the role of HB-EGF in the context of reduced nitric oxide bioavailability in diabetic nephropathy.
- To elucidate the relationship between endothelial nitric oxide synthase (eNOS) deficiency, diabetes, and HB-EGF expression.
- To determine if HB-EGF mediates renal injury in experimental diabetic nephropathy.
Main Methods:
- Utilized endothelial nitric oxide synthase (eNOS)-knockout and eNOS-knockout diabetic (Lepr(db/db)) mouse models.
- Measured HB-EGF expression in kidney tissues and urine.
- Employed nitric oxide synthase inhibitors (L-NAME) and NO replenishment (sodium nitrate).
- Investigated the effect of endothelial-specific HB-EGF deletion on renal injury.
Main Results:
- HB-EGF expression was elevated in the kidneys of eNOS-knockout and diabetic eNOS-knockout mice.
- Renal HB-EGF levels increased with glomerulopathy progression in diabetic eNOS-knockout mice.
- Nitric oxide synthase inhibition increased HB-EGF expression, while NO replenishment reduced it.
- Endothelial HB-EGF deletion attenuated renal injury in diabetic eNOS-knockout mice.
Conclusions:
- Reduced nitric oxide bioavailability leads to increased HB-EGF expression in the diabetic kidney.
- HB-EGF appears to be a key mediator of progressive diabetic nephropathy in the absence of eNOS.
- Targeting HB-EGF may offer a therapeutic strategy for diabetic nephropathy associated with impaired NO signaling.
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