The role of Sgk-1 in mediating peroxisome proliferator activated receptor gamma induced sodium transport and water transport in human proximal tubule cells
Background: Cellular sodium and water transport are dysregulated in diabetes mellitus. We have recently demonstrated that serum and glucocorticoid regulated kinase (Sgk) regulates high glucose-induced proximal tubular cell (PTC) Na reabsorption via the sodium-hydrogen exchanger-3 (NHE3) and the epidermal growth factor-receptor (EGF-R). Peroxisome proliferator-activator gamma (PPARg) agonists, including thiazolidinediones, are used in patients with diabetes, but their use is limited by fluid retention. Recent data suggests that PPARg agonists stimulate both Sgk and EGF-R activity and increases aquaporin (AQP) expression in the distal tubule. However, the effects of PPARg agonists on Sgk1 and AQP expression, and on sodium and water retention in the proximal tubule are not known.
Aim: To determine the roles of Sgk-1 in high glucose and PPARg agonist mediated sodium and water retention in human PTCs.
Methods: PTCs were exposed to 5 mM, 25mM glucose or 3µM pioglitazone. Sgk1, NHE3, PPARg and AQP1 mRNA and protein expression were measured by semi quantitative PCR and Western blot. The role of Sgk1 was elucidated by effectively silencing Sgk1 using SiRNA techniques.
Results: Exposure of PTCs to both high glucose and pioglitazone increased mRNA and protein expression of NHE3 (both P<0.05), Sgk1 (both P<0.05) and PPARg (both P<0.05). AQP1-9 was expressed in PTC. AQP1 mRNA was induced by pioglitazone (P<0.01), which was abolished when Sgk1 was silenced.
Conclusions: Sgk-1 is likely to mediate PPARg induced Na reabsorption via NHE3 and water reabsorption via AQP1 channels in the proximal tubule.