NOD2 promotes endothelial-to-mesenchymal transition of glomerular endothelial cells via MEK/ERK signaling pathway in diabetic nephropathy.

Endothelial-to-mesenchymal transition (EndMT) of glomerular vascular endothelial cells (GEnCs) is now considered to play a critical role in diabetic nephropathy (DN). NOD2 is newly discovered to be closely related to DN renal injury. However, the relationship between NOD2 and EndMT of GEnCs has never been reported. In the present study, we found that NOD2 over-expression was positively correlated with the severity of DN injury in human renal biopsy samples. Immunohistochemical staining of DN renal slices showed gradual absence of endothelial character and gain of mesenchymal character, both of which were associated with NOD2 over-expression. In high glucose stimulated GEnCs, NOD2 was increased. What's more, over-expression and activation of NOD2 could both promote EndMT of GEnCs. On the other hand, silencing of NOD2 markedly attenuated EndMT induced by high glucose. Mechanically, we further found that MEK/ERK signaling pathway was involved in NOD2-regulated EndMT. Collectively, our results indicate that NOD2 has a regulatory role in EndMT via activation of MEK/ERK in high glucose-treated GEnCs. Targeting this pathway is a promising strategy for intervention of DN endothelial dysfunction.