Aldosterone Regulates Cellular Turnover and Mitogen-Activated Protein Kinase Family Expression in the Neonatal Rat Kidney

초록

Growing evidence indicates that aldosterone is a potent mitogenic signal regulating genes involved in antiapoptosis, cell proliferation and growth. We investigated the role of endogenous aldosterone in renal development, cell proliferation and apoptosis, and mitogen-activated protein kinase (MAPK) family expression. Newborn rats were treated with either spironolactone (200 mg/kg/d) in olive oil or only olive oil for 7 days. TUNEL assay and proliferating cell nuclear antigen (PCNA) stain were per-formed on kidney sections. Immunoblots, immunohistochemical (IHC) stain, and reverse transcriptase-PCR for MAPKs were performed. PCNA-positive proliferating cells decreased and apoptotic cells increased significantly with spironolactone (P < 0.05). In the spironolactone-treated group, c-jun N-terminal kinase (JNK)-2 expression increased, whereas extracellular signal regulated kinase (ERK)-2 and p38 expressions decreased in immunoblots (P < 0.05) and IHC stain. ERK-2 and p38 mRNA expressions increased in the spironolactone-treated group (P < 0.05). This study demonstrates that aldosterone blockade in the developing kidney decreases cellular proliferation, increases apoptosis, and modulates the expressions of JNK-2, ERK-2, and p38. Aldosterone possibly participates in renal development and MAPK family may serve as, in part, the signaling intermediate through the mineralocorticoid receptor (MR) in the developing kidney.

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