TY - JOUR
T1 - Angiotensin inhibition in the developing kidney; tubulointerstitial effect
AU - Yoo, Kee Hwan
AU - Yim, Hyung Eun
AU - Bae, Eun Soo
AU - Hong, Young Sook
N1 - Publisher Copyright:
© 2019, International Pediatric Research Foundation, Inc.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Background: Renin-angiotensin system (RAS) blockade during nephrogenesis causes a broad range of renal mal-development. Here, we hypothesized that disruption of renal lymphangiogenesis may contribute to tubulointerstitial alterations after RAS blockade during kidney maturation. Methods: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for 7 days after birth. Lymphangiogenesis was assessed via immunostaining and/or immunoblots for vascular endothelial growth factor (VEGF)-C, VEGF receptor (VEGFR)−3, Podoplanin, and Ki-67. The intrarenal expression of fibroblast growth factor (FGF)−1, FGF-2, FGF receptor (R)−1, α-smooth muscle actin (α-SMA), and fibroblast-specific protein (FSP)−1 was also determined. Sirius Red staining was performed to evaluate interstitial collagen deposition. Results: On postnatal day 8, renal lymphangiogenesis was disrupted by neonatal enalapril treatment. The expression of podoplanin and Ki-67 decreased in enalapril-treated kidneys. While the expression of VEGF-C was decreased, the levels of VEGFR-3 receptor increased following enalapril treatment. Enalapril treatment also reduced the renal expression of FGF-1, FGF-2, and FGFR-1. Enalapril-treated kidneys exhibited profibrogenic properties with increased expression of α-SMA and FSP-1 and enhanced deposition of interstitial collagen. Conclusion: Enalapril treatment during postnatal renal maturation can disrupt renal lymphangiogenesis along with tubulointerstitial changes, which may result in a pro-fibrotic environment in the developing rat kidney.
AB - Background: Renin-angiotensin system (RAS) blockade during nephrogenesis causes a broad range of renal mal-development. Here, we hypothesized that disruption of renal lymphangiogenesis may contribute to tubulointerstitial alterations after RAS blockade during kidney maturation. Methods: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for 7 days after birth. Lymphangiogenesis was assessed via immunostaining and/or immunoblots for vascular endothelial growth factor (VEGF)-C, VEGF receptor (VEGFR)−3, Podoplanin, and Ki-67. The intrarenal expression of fibroblast growth factor (FGF)−1, FGF-2, FGF receptor (R)−1, α-smooth muscle actin (α-SMA), and fibroblast-specific protein (FSP)−1 was also determined. Sirius Red staining was performed to evaluate interstitial collagen deposition. Results: On postnatal day 8, renal lymphangiogenesis was disrupted by neonatal enalapril treatment. The expression of podoplanin and Ki-67 decreased in enalapril-treated kidneys. While the expression of VEGF-C was decreased, the levels of VEGFR-3 receptor increased following enalapril treatment. Enalapril treatment also reduced the renal expression of FGF-1, FGF-2, and FGFR-1. Enalapril-treated kidneys exhibited profibrogenic properties with increased expression of α-SMA and FSP-1 and enhanced deposition of interstitial collagen. Conclusion: Enalapril treatment during postnatal renal maturation can disrupt renal lymphangiogenesis along with tubulointerstitial changes, which may result in a pro-fibrotic environment in the developing rat kidney.
UR - http://www.scopus.com/inward/record.url?scp=85060935067&partnerID=8YFLogxK
U2 - 10.1038/s41390-019-0288-9
DO - 10.1038/s41390-019-0288-9
M3 - Article
C2 - 30700837
AN - SCOPUS:85060935067
SN - 0031-3998
VL - 85
SP - 724
EP - 730
JO - Pediatric Research
JF - Pediatric Research
IS - 5
ER -