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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

EP4 inhibition attenuates the development of diabetic and non-diabetic experimental kidney disease

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Author(s):
Thieme, Karina ; Majumder, Syamantak ; Brijmohan, Angela S. ; Batchu, N. ; Bowskill, Bridgit B. ; Alghamdi, Tamadher A. ; Advani, Suzanne L. ; Kabir, M. Golam ; Liu, Youan ; Advani, Andrew
Total Authors: 10
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, JUN 13 2017.
Web of Science Citations: 5
Abstract

The therapeutic targeting of prostanoid subtype receptors may slow the development of chronic kidney disease (CKD) through mechanisms that are distinct from those of upstream COX inhibition. Here, employing multiple experimental models of CKD, we studied the effects of inhibition of the EP4 receptor, one of four receptor subtypes for the prostanoid prostaglandin E-2. In streptozotocin-diabetic endothelial nitric oxide synthase knockout mice, EP4 inhibition attenuated the development of albuminuria, whereas the COX inhibitor indomethacin did not. In Type 2 diabetic db/db mice, EP4 inhibition lowered albuminuria to a level comparable with that of the ACE inhibitor captopril. However, unlike captopril, EP4 inhibition had no effect on blood pressure or hyperfiltration although it did attenuate mesangial matrix accumulation. Indicating a glucose-independent mechanism of action, EP4 inhibition also attenuated proteinuria development and glomerular scarring in non-diabetic rats subjected to surgical renal mass ablation. Finally, in vitro, EP4 inhibition prevented transforming growth factor-beta 1 induced dedifferentiation of glomerular podocytes. In rodent models of diabetic and non-diabetic CKD, EP4 inhibition attenuated renal injury through mechanisms that were distinct from either broadspectrum COX inhibition or ``standard of care{''} renin angiotensin system blockade. EP4 inhibition may represent a viable repurposing opportunity for the treatment of CKD. (AU)

FAPESP's process: 16/04591-1 - Non-coding RNAs in diabetic kidney disease
Grantee:Karina Thieme
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor