title: NOD2 promotes endothelial-to-mesenchymal transition of glomerular endothelial cells via MEK/ERK signaling pathway in diabetic nephropathy.
abstract: 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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: 13938525666@139.com.
authors.forename: Zhanzheng
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D003928:Diabetic Nephropathies; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D020935:MAP Kinase Signaling System; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D005947:Glucose
keywords: Diabetic nephropathy; ERK; Endothelial-to-mesenchymal transition; Glomerular endothelial cells; NOD2