An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice

Figure 5

Telmisartan suppressed the podocyte apoptosis which was induced by angiotensin II. The effects of AII as well as telmisartan on the podocytes apoptosis were examined by the flow cytometry or by the Hoechst staining. (a, b) The podocytes were treated with 10⁻⁶M AII in the presence or absence of 10⁻⁶M telmisartan or 5 mM γ-secretase inhibitor (GSI) for 72 h. Apoptosis in podocytes was determined by low propidium iodide staining and prominent annexin V labeling using the flow cytometry. AII significantly induced podocytes apoptosis compared to the controls (12.56±1.9% versus 7.09±1.4%). Telmisartan significantly suppressed AII-induced apoptosis in podocytes (8.51±2.0% versus 12.56±1.9%). GSI also significantly suppressed that (7.89±1.6% versus 12.56±1.9%). Representative results of three independent experiments were presented. *𝑃<0.05, **𝑃<0.01. (c) The apoptosis in podocytes was examined by Hoechst staining. The podocytes were treated with 10⁻⁶M AII, 10⁻⁶M telmisartan, and 5 mM GSI as indicated in the figures for 72 h. Apoptosis was determined by nuclear condensation pattern and expressed as the percentage of apoptotic cells per high-power field. A total of 5 high-power fields in a pericentric distribution were quantitated per well. (d) Telmisartan and GSIs suppressed the podocyte apoptosis (CT 2.3±1.5%, AII 22.3±2.54%, Telm + AII 6.3±0.9%, and GSI + AII 3.6±2.0, resp.). Telm: telmisartan, **𝑃<0.01. (e) Schematic illustration of the effects of telmisartan on the Notch pathway in podocytes.