Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy.
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.
Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan; Department of Nephrology, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan; Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Yu
Y
Tateishi
Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan.
Mayuko
M
Osada-Oka
Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Masako
M
Tanaka
Department of Pharmacology, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Masayuki
M
Shiota
Department of Pharmacology, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Yasukatsu
Y
Izumi
Department of Nephrology, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Eiji
E
Ishimura
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Koka
K
Motoyama
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Masaaki
M
Inaba
Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan. Electronic address: miura-pha@med.osaka-cu.ac.jp.
Katsuyuki
K
Miura
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014517:Ureteral Obstruction / Q000235:genetics* / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D055513:Connective Tissue Growth Factor; D003094:Collagen
Hypoxia-inducible factor; Macrophage; Renal fibrosis