Angiotensin Converting Enzyme Inhibition Modulates Mitogen Activated Protein Kinase Family Expressions in the Neonatal Rat Kidney / 소아과

ABSTRACT

PURPOSE: In a developing kidney, the renin-angiotensin system(RAS) is markedly activated and is thought to play an important role in postnatal renal growth and maturation. We previously demonstrated that angiotensin converting enzyme(ACE) inhibition in a developing rat kidney increases apoptosis and decreases its related gene expressions, which may account for renal growth impairment. Among the mitogen-activated protein kinases(MAPK) family members, c-jun N terminal kinase(JNK) and p38 MAPK(p38) are thought to inhibit cell growth and induce apoptosis. This study was designed to investigate the relationship between the RAS and the MAPK family during neonatal renal development. METHODS: Forty-nine neonatal Spargue-Dawley rats were separated into two groups. The enalapril group was treated with ACE inhibitor(enalapril30 mg/kg/day) and the control group with normal saline for seven days. Their kidneys were removed for immunohistochemical stain and western blot analysis of JNK-2 and p38. RESULTS: In the enalapril group, JNK-2 expression was strongly detected in the dilated cortical tubular epithelial cells, and JNK-2 protein expression was significantly increased compared to the control group. p38 expression was noted in the dilated tubular epithelial cells by ACE inhibitor and also p38 protein expression was significantly increased. CONCLUSION: These results suggest that the expressions of the MAPK family, especially JNK and p38, are modulated by ACE inhibition in the neonatal rat kidney. In regard of the correlation between MAPK activations and the occurrence of apoptosis in renal growth impairment by ACE inhibition, JNK and p38 may be implicated to participate in angiotensin II related intracellular signaling pathways of renal apoptosis in developing kidney.