We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Low nitric oxide bioavailability upregulates renal heparin binding EGF-like growth factor expression.
- Authors
Miyazawa, Tomoki; Zeng, Fenghua; Wang, Suwan; Fan, Xiaofeng; Cheng, Huifang; Yang, Haichun; Bian, Aihua; Fogo, Agnes B; Harris, Raymond C
- Abstract
Decreased nitric oxide bioavailability has an important role in the initiation and progression of diabetic nephropathy, but the underlying mechanisms remain unclear. Here, we found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression levels increased in the kidneys of both endothelial nitric oxide synthase (eNOS)-knockout and eNOS-knockout diabetic (Leprdb/db) mice as early as at 8 weeks of age. Further increases in expression were only seen in eNOS-knockout diabetic mice and paralleled the progression of glomerulopathy. HB-EGF expression increased in endothelium, podocytes, and tubular epithelial cells. In cultured glomerular endothelial cells, the nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or L-N5-(1-iminoethyl) ornithine increased HB-EGF protein expression. Administration of L-NAME dramatically increased renal HB-EGF expression and urinary HB-EGF excretion in diabetic mice. On the other hand, replenishing nitric oxide with sodium nitrate in eNOS-knockout diabetic mice reduced urinary HB-EGF excretion and inhibited the progression of diabetic nephropathy. Furthermore, specific deletion of HB-EGF expression in the endothelium attenuated renal injury in diabetic eNOS-knockout mice. Thus, our results suggest that decreased nitric oxide bioavailability leads to increased HB-EGF expression, which may be an important mediator of the resulting progressive diabetic nephropathy in eNOS-knockout diabetic mice.
- Subjects
NITRIC oxide; BIOAVAILABILITY; HEPARIN; EPIDERMAL growth factor; NITRIC-oxide synthases
- Publication
Kidney International, 2013, Vol 84, Issue 6, p1176
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2013.214