The implication of Numb-induced Notch signaling in endothelial-mesenchymal transition of diabetic nephropathy

Aim: This study was purposed to figure out the contribution of Numb-induced Notch signaling to the development of diabetic nephropathy (DN). Methods: Two hundred and twenty six DN patients were included, and human glomerular endothelial cells (RGEC) were cultured. MSCV-Numb-IRES-GFP, MSCV-Notch1-IRES-GFP and MSCV-Hes1-IRES-GFP were transfected to construct the recombinant retroviral vectors. Result: The over-expressed Numb and Notch1, as well as the under-expressed Hes-1 were correlated with the undesirable prognosis of DN patients (P < 0.05). Within the cell lines transfection with si-Numb would cut down E-cadherin and CD31 expressions (P < 0.05), yet elevated alpha-SMA and vimentin expressions (P < 0.05). The apoptotic rate of si-Numb cell lines underperformed ones categorized into the hyperglucose group (P < 0.05), whereas the lowly-expressed Notchl and Hest were observably associated with inhibited proliferation of myofibroblasts (P < 0.05). Addition of ADPT caused under-expressed alpha-SMA and vimentin, along with the over-expressed E-cadherin and CD31 (P < 0.05). Silencing of Notchl and Hesl reversed the epithelial-mesenchymal transition (EMT) process that was triggered by high glucose (P < 0.05). Conclusion: Numb negatively regulated Notch signaling pathway in EMT of DN, implying that they had great potentials to serve as therapeutic targets or diagnostic biomarkers for DN. (C) 2018 Published by Elsevier Inc.