Modulation of nephrin in the diabetic kidney: association with systemic hypertension and increasing albuminuria

Forbes, Josephine M., Bonnet, Fabrice, Russo, Leileata M., Burns, Wendy C., Cao, Zemin, Candido, Riccardo, Kawachi, Hiroshi, Allen, Terri J., Cooper, Mark E., Jerums, George and Osicka, Tanya M. (2002) Modulation of nephrin in the diabetic kidney: association with systemic hypertension and increasing albuminuria. Journal of Hypertension, 20 5: 985-992. doi:10.1097/00004872-200205000-00034


Author Forbes, Josephine M.
Bonnet, Fabrice
Russo, Leileata M.
Burns, Wendy C.
Cao, Zemin
Candido, Riccardo
Kawachi, Hiroshi
Allen, Terri J.
Cooper, Mark E.
Jerums, George
Osicka, Tanya M.
Title Modulation of nephrin in the diabetic kidney: association with systemic hypertension and increasing albuminuria
Journal name Journal of Hypertension   Check publisher's open access policy
ISSN 0263-6352
1473-5598
Publication date 2002-05
Sub-type Article (original research)
DOI 10.1097/00004872-200205000-00034
Open Access Status Not yet assessed
Volume 20
Issue 5
Start page 985
End page 992
Total pages 8
Place of publication London, United Kingdom
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objective: Nephrin, a cytoskeletal protein which localizes to the slit pore of podocytes, may play a role in proteinuria. This study examines the possible relationship between nephrin expression and albuminuria in normotensive and hypertensive diabetic rats.

Methods: Streptozotocin diabetes was induced in both Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Diabetic and control animals were sacrificed and the kidneys obtained after 8, 16 and 24 weeks. The glomerular filtration rate (GFR) and albuminuria were also measured. Glycaemic control was assessed by measurement of plasma glucose and glycated haemoglobin (HbA1c). Nephrin gene expression was quantitated by real-time polymerase chain reaction (PCR) and localized by in situ hybridization. Nephrin protein expression was localized by immunohistochemistry and quantitated.

Results: Following a transient rise at 8 weeks in the diabetic SHR (P < 0.05 versus control SHRs), nephrin gene expression, as determined by real-time PCR, was significantly decreased at 16 and 24 weeks (P < 0.05 versus control SHRs). In situ hybridization confirmed similar changes in nephrin gene expression, which were confined to the glomeruli. This reduction in glomerular nephrin gene expression was associated with increasing albuminuria at 16 and 24 weeks in diabetic SHRs. There were no significant changes in nephrin gene expression, either by real-time reverse transcription polymerase chain reaction or in situ hybridization, observed in normotensive diabetic WKY rats, in the context of much less albuminuria in this group. Immunohistochemistry for nephrin protein revealed a greater depletion in renal nephrin content in SHR than in WKY rats after 24 weeks of diabetes.

Conclusion: Reduction in renal nephrin gene and protein expression is closely associated with the development of albuminuria, as observed in an experimental model of diabetes and hypertension.
Keyword Diabetes
Diabetic nephropathy
Hypertension
Nephrin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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