Protease activated receptor 2 in diabetic nephropathy: A double edged sword

Maaike Waasdorp*, JanWillem Duitman, Sandrine Florquin, C. Arnold Spek

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Diabetic nephropathy is a major microvascular complication of diabetes mellitus, and the leading cause of end stage renal disease worldwide. The pathogenesis of diabetic nephropathy is complex, making the development of novel treatments that stop or reverse the progression of microalbuminuria into end stage renal disease a challenge. Protease activated receptor (PAR)-2 has recently been shown to aggravate disease progression in diabetic nephropathy based upon which it was suggested that PAR-2 would be a potential target for the treatment of diabetic nephropathy. To fully appreciate the translational potential of PAR-2 in diabetic nephropathy, we evaluated the effect of PAR-2 deficiency on the development of diabetic nephropathy in a streptozotocin-induced diabetes model characteristic of type 1 diabetes. Although diabetic PAR-2 deficient mice showed reduced albuminuria compared to diabetic wild type mice, an increase in mesangial expansion was evident in the PAR-2 deficient mice. No differences were observed in blood glucose levels, podocyte numbers or in glomerular vascular density. These results show that PAR-2 plays a dual role in the development of streptozotocin-induced diabetic nephropathy and may thus not be the eagerly awaited novel target to combat diabetic nephropathy. Targeting PAR-2 should consequently only be pursued with great care in a clinical setting.

Original languageEnglish
Article numberAJTR0059527
Pages (from-to)4512-4520
Number of pages9
JournalAmerican Journal of Translational Research
Volume9
Issue number10
Publication statusPublished - 15 Oct 2017
Externally publishedYes

Cite this

Waasdorp, M., Duitman, J., Florquin, S., & Spek, C. A. (2017). Protease activated receptor 2 in diabetic nephropathy: A double edged sword. American Journal of Translational Research, 9(10), 4512-4520. [AJTR0059527].