Background: Inflammation plays a key role in the development and progression of diabetic nephropathy. KCa3.1, a potassium channel protein, is associated with vascular inflammation, atherogenesis, and proliferation of endothelial cells, macrophages, and fibroblasts. Blockade of KCa3.1 has been shown to ameliorate renal fibrosis in diabetic nephropathy through TGF-β1 pathway. However, the role of KCa3.1 in the inflammatory responses of diabetic nephropathy is unknown.

Aim: To investigate the role of KCa3.1 in the inflammatory responses of diabetic nephropathy.

Methods: Two animal models were used in this study: (1) wild type KCa3.1+/+ and KCa3.1-/- mice were induced with STZ, and (2) eNOS-/- mice were induced by STZ, and then treated with or without a selective inhibitor of KCa3.1 (TRAM34). After mice were sacrificed, proinflammatory cytokines Chemokine (C-C motif) ligand 20 (CCl20), IL-6 and TNF-α were examined by real time PCR and immunohistochemistry staining. The marker of inflammation CD68 were measured by immunohistochemistry staining as well as NF- kB signalling pathway.

Results: Both mRNA and protein levels of CCL20, IL-6 and TNF-α significantly decreased in kidneys of diabetic KCa3.1-/- mice compared to diabetic wild type mice. Similarly, TRAM34 reduced the expression of inflammatory markers described above in diabetic eNOS-/- mice compared to diabetic vehicle groups. Furthermore, blocking the KCa3.1 channel in both animal models led to the reduction of phosphorylation of NF-kB.

Conclusions: KCa3.1 mediated renal inflammation under diabetic condition through NF-kB pathway.