Angiotensin inhibition in the developing kidney; tubulointerstitial effect

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

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)


    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
    Pages (from-to)724-730
    Number of pages7
    JournalPediatric Research
    Issue number5
    Publication statusPublished - 2019 Apr 1

    Bibliographical note

    Publisher Copyright:
    © 2019, International Pediatric Research Foundation, Inc.

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health


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