Angiotensin inhibition in the developing kidney; tubulointerstitial effect

Kee Hwan Yoo, Hyung-Eun Yim, Eun Soo Bae, Young Sook Hong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalPediatric Research
DOIs
Publication statusPublished - 2019 Jan 1

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Angiotensins
Enalapril
Kidney
Lymphangiogenesis
Vascular Endothelial Growth Factor C
Fibroblast Growth Factor 1
Fibroblast Growth Factor 2
Renin-Angiotensin System
Collagen
Vascular Endothelial Growth Factor Receptor-3
Receptor, Fibroblast Growth Factor, Type 1
Smooth Muscle
Actins
Parturition
Staining and Labeling

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Angiotensin inhibition in the developing kidney; tubulointerstitial effect. / Yoo, Kee Hwan; Yim, Hyung-Eun; Bae, Eun Soo; Hong, Young Sook.

In: Pediatric Research, 01.01.2019.

Research output: Contribution to journalArticle

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