The PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats

Objectives. The present study aimed to investigate the relationship between PI3K/p-Akt signaling pathway and podocyte impairment in DN rats as well as the protective effect of calcitriol. Methods. SD rats were randomly divided into four groups: normal control (NC), normal treated with calcitriol (NC + VD), diabetic nephropathy (DN) and DN treated with calcitriol (DN + VD); all VD rats were treated with 0.1 mu g/kg/d calcitriol by gavage. DN model rats were established by intraperitoneal injections of streptozotocin (STZ). Rats were sacrificed after 18 weeks of treatments. Results. In the present study, increased albuminuria was observed as early as 3 weeks of diabetes and continued to increase more than six-fold throughout the length of the study (18 weeks). Expectedly, animals receiving the treatment with calcitriol was protected from this increase, lower about one third. Meanwhile, the expression of podocyte specific markers, including nephrin and podocin, together with PI3K/p-Akt was significantly decreased in DN rats, whereas calcitriol reversed these above changes accompanied by elevated the expression levels of VDR. Additionally, a positive correlation was observed between the expression levels of nephrin and VDR (r = 0.776, P < 0.05). Likewise, the expression of nephrin was positively correlated with both PI3K-p85 and p-Akt (r = 0.736, P < 0.05; r = 0.855, P < 0.05, respectively). Conclusion. PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats. The manipulation of calcitriol might act as a promising therapeutic intervention for diabetic nephropathy. (C) 2014 Elsevier Inc. All rights reserved.