Aldosterone induces apoptosis via the Wnt signalling pathway

Evidence suggests that aldosterone (ALD) is involved in glomerular damage; however, it is rarely known whether ALD exerts a direct injurious effect on mesangial cells (MC). The objectives of this study were to determine the relationship between ALD and apoptosis, and investigate the cell signalling pathway by which ALD induces apoptosis. Rat MC were treated with ALD (10-8, 10-7 or 10-6 M) for 24 h. In some experiments, MC were pretreated with 10-7 M spironolactone or 10-2 M LiCl for 1 h. Apoptosis was quantified using Annexin V-propidium iodide staining and flow cytometry, and caspase 3 activity was analysed. Gene and protein expression were quantified using quantitative real-time PCR and Western blotting, respectively. ALD directly induced apoptosis in MC in a caspase dependent manner. More importantly, Wnt signalling was involved in ALD-induced cell apoptosis. ALD suppressed the Wnt signalling pathway in MC, leading to downregulation of Wnt4 and Wnt5a mRNA expression, increased GSK-3β protein expression and reduced β-catenin protein expression. A competitive antagonist of ALD, spironolactone (SPI), attenuated the ability of ALD to inhibit Wnt signalling. The Wnt signalling agonist, LiCl, inhibited ALD-induced apoptosis. This study suggests that ALD may directly induce apoptosis in MC via the Wnt signalling pathway. Modulation of Wnt signal transduction may be beneficial for enhancing mesangial cell survival in renal injury. Key words: Aldosterone, apoptosis, β-catenin, GSK-3β, mesangial cells.