The implication of Numb-induced Notch signaling in endothelial-mesenchymal transition of diabetic nephropathy.
This study was purposed to figure out the contribution of Numb-induced Notch signaling to the development of diabetic nephropathy (DN). 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. 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 α-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 Notch1 and Hes1 were observably associated with inhibited proliferation of myofibroblasts (P < 0.05). Addition of ADPT caused under-expressed α-SMA and vimentin, along with the over-expressed E-cadherin and CD31 (P < 0.05). Silencing of Notch1 and Hes1 reversed the epithelial-mesenchymal transition (EMT) process that was triggered by high glucose (P < 0.05). 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.