Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy

Yu Tateishi, Mayuko Osada-Oka, Masako Tanaka, Masayuki Shiota, Yasukatsu Izumi, Eiji Ishimura, Koka Motoyama, Masaaki Inaba, Katsuyuki Miura

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10 Citations (Scopus)

Abstract

Hypoxia-inducible factors (HIFs) play an important role in the pathogenesis of renal fibrosis. Although the role of macrophage infiltration in the progression of renal fibrosis is well known, the role of macrophage HIF-1 remains to be revealed. To address this question, myeloid specific conditional HIF-1 knock out mice were subjected to unilateral ureteral obstruction (UUO). Renal interstitial deposition of collagen III and mRNA expressions of collagen I and collagen III were markedly increased at 7 days after UUO and myeloid HIF-1 depletion significantly accelerated these increases. Immunohistochemistry and flow cytometric analysis revealed that renal infiltrating macrophages were increased with duration of UUO but myeloid HIF-1 depletion did not affect these changes. Myeloid HIF-1 depletion did not affect M1 and M2 macrophage phenotype polarization in obstructed kidneys. Renal connective tissue growth factor (CTGF) expression was markedly increased and myeloid HIF-1 depletion further enhanced this increase. Immunomagnetic separation of renal cells revealed that renal CTGF was expressed predominantly in renal cells other than macrophages. It is suggested that myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive kidney. Alteration of CTGF expression in renal cells other than macrophages is one of possible mechanisms by which myeloid HIF-1 protected renal fibrosis.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalJournal of Pharmacological Sciences
Volume127
Issue number2
DOIs
Publication statusPublished - 2015
Externally publishedYes

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Keywords

  • Hypoxia-inducible factor
  • Macrophage
  • Renal fibrosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Tateishi, Y., Osada-Oka, M., Tanaka, M., Shiota, M., Izumi, Y., Ishimura, E., Motoyama, K., Inaba, M., & Miura, K. (2015). Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy. Journal of Pharmacological Sciences, 127(2), 181-189. https://doi.org/10.1016/j.jphs.2014.12.011