Effects of thromboxane prostanoid receptor deficiency on diabetic nephropathy induced by high fat diet and streptozotocin in mice.

Diabetic nephropathy (DN), one of the main causes of end-stage renal disease, still remains as a challenge of clinical management. This study aimed to determine whether deficiency of the thromboxane (TX) prostanoid receptor (TP), which mediates the contractile activities of all prostanoids, alleviates the development of DN and if so, to examine the underlying mechanism(s). Diabetes was induced by high fat diet and streptozotocin injection in wild-type (WT) mice and those with TP deficiency (TP). Here we show that WT and TP mice developed diabetes with a similar blood glucose level; however, signs of renal functional impairments and pathologies occurred to a lesser extent in TP than in WT mice. Also, the extent of an increase in the expression level of transforming growth factor-β1 (TGF-β1), a common pathological mediator of DN, in diabetic renal cortexes of TP mice was lower than that of WT counterparts. Moreover, we noted that expression levels of cyclooxygenase (COX)-2 and calcium-dependent phospholipase A (cPLA) as well as levels of prostaglandin E and TXA in diabetic renal cortexes were increased as compared to those of non-diabetic conditions. These results thus demonstrate that possibly due to up-regulated cPLA and COX-2 that lead to increased prostanoid syntheses in diabetic renal cortexes, TP alleviates DN development. In addition, our results suggest that such an effect of TP might be related to the suppression of TGF-β1 up-regulation that is commonly associated with the disease condition.