TY - JOUR
T1 - ACE inhibition modulates transforming growth factor-β receptors in the young rat
AU - Kang, Nam Soo
AU - Yim, Hyung Eun
AU - Bae, In Sun
AU - Choi, Jeong Hoon
AU - Choi, Byung Min
AU - Yoo, Kee Hwan
AU - Hong, Young Sook
AU - Lee, Joo Won
AU - Kim, Soon Kyum
PY - 2003/9/1
Y1 - 2003/9/1
N2 - The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-β1 (TGF-β1), TGF-β receptor I [TβRI, activin-like kinase (ALK)-1 and ALK-5], and TGF-β receptor II (TβRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-β1, ALK-1, ALK-5, and TβRII, and for RT-PCR of ALK-5 and TβRII TGF-β1, ALK-1, ALK-5, and TβRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight (P<0.05 versus vehicle). Enalapril decreased renal TGF-β1, ALK-1, and ALK-5 protein expression (P<0.05). Also, enalapril decreased ALK-5 mRNA expression (P<0.05). TβRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-β1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TβRII may not be modulated by ACE inhibition in the developing kidney.
AB - The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-β1 (TGF-β1), TGF-β receptor I [TβRI, activin-like kinase (ALK)-1 and ALK-5], and TGF-β receptor II (TβRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-β1, ALK-1, ALK-5, and TβRII, and for RT-PCR of ALK-5 and TβRII TGF-β1, ALK-1, ALK-5, and TβRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight (P<0.05 versus vehicle). Enalapril decreased renal TGF-β1, ALK-1, and ALK-5 protein expression (P<0.05). Also, enalapril decreased ALK-5 mRNA expression (P<0.05). TβRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-β1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TβRII may not be modulated by ACE inhibition in the developing kidney.
KW - Angiotensin converting enzyme inhibitors
KW - Renin-angiotensin system
KW - Transforming growth factor β receptor
KW - Transforming growth factor β1
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U2 - 10.1007/s00467-003-1220-3
DO - 10.1007/s00467-003-1220-3
M3 - Article
C2 - 12883979
AN - SCOPUS:0141746388
VL - 18
SP - 865
EP - 871
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
IS - 9
ER -