Overall, we thus show that PAR-1 inhibition reduces blood glucose levels during the progression of diabetic nephropathy in experimental type 2 diabetes but does not improve renal function.
PAR2 promotes cytokine production through mitogen-activated protein kinase or nuclear factor kappa B signaling, and previous reports demonstrated that inhibition of PAR2 alleviated kidney injuries such as diabetic kidney disease and renal fibrosis in animal models.
These data indicate that PXR is upregulated in the diabetic kidney with aberrant epigenetic modifications and may modulate the course of diabetic kidney disease through the activation of these genes.
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.