Inflammation and reactive oxygen species (ROS) play crucial roles in the progression of chronic kidney diseases. Vitamin D has been shown anti-inflammatory effects, but the underlying mechanism is not fully understood. Here, we investigated whether calcitriol exerts protective effects via upregulating A20 in angiotensinII (AngII)-induced renal injury. Male C57BL/6 mice were infused with vehicle or AngII for 10 days. Calcitriol reduced infiltration of T lymphocytes and macrophages. This reduction of inflammatory cells was accompanied by elevated A20 and decreased pro-inflammatory cytokines (PICs) and reactive oxygen species (ROS). Calcitriol could inhibit NF-κB activation and necroptotic pathway. Induction of A20 was located primarily to the tubular epithelial cells. In rat proximal tubular epithelial cells (NRK-52E), calcitriol stably upregulated A20 and reduced the PICs and ROS. Inhibitory effect of A20 on PICs and ROS depended on suppressing NF-κB pathway and necroptotic pathway, respectively. A20 knockdown diminished the effect of calcitriol on suppressing NF-κB and necroptotic pathways. However, A20 deficiency could not abrogate the inhibitory effect of calcitriol on NF-κB and necroptotic pathways. Our results established that A20 is involved in the renoprotective effect by calcitriol via negatively modulating the NF-κB pathway and necroptotic pathway in AngII-induced renal injury.
Keywords: A20; NF-κB; ROS; angiotensinII (AngII); calcitriol; inflammation.