Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: Special references to HIF-1 dependent gene expression of profibrogenic molecules

Kazuya Kabei, Yu Tateishi, Masakazu Nozaki, Masako Tanaka, Masayuki Shiota, Mayuko Osada-Oka, Shunji Nishide, Junji Uchida, Tatsuya Nakatani, Shuhei Tomita, Katsuyuki Miura

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO. Various factors promoting fibrosis were up-regulated during the development of fibrosis. HIF-1 dependent gene expression of profibrotic molecules, plasminogen activator inhibitor 1, connective tissue growth factor, lysyl oxidase like 2 and transglutaminase 2 was observed in the obstructed kidney but such HIF-1 dependency was limited to the early onset of renal fibrosis. Global HIF-1 deletion tended to attenuate interstitial collagen I deposition at 3 days but had no effects thereafter. It is suggested that HIF-1 dependent profibrogenic mechanisms are operating at the early onset of renal fibrosis but its contribution declines with the progression in mouse UUO model.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalJournal of Pharmacological Sciences
Volume136
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Hypoxia-Inducible Factor 1
Fibrosis
Kidney
Gene Expression
Ureteral Obstruction
Tamoxifen
Ubiquitin C
Protein-Lysine 6-Oxidase
Connective Tissue Growth Factor
Facilitative Glucose Transport Proteins
Plasminogen Activator Inhibitor 1
Transcriptome
Up-Regulation
Collagen
Alleles

Keywords

  • HIF-1α
  • Hypoxia
  • Hypoxia-inducible factor
  • Renal fibrosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney : Special references to HIF-1 dependent gene expression of profibrogenic molecules. / Kabei, Kazuya; Tateishi, Yu; Nozaki, Masakazu; Tanaka, Masako; Shiota, Masayuki; Osada-Oka, Mayuko; Nishide, Shunji; Uchida, Junji; Nakatani, Tatsuya; Tomita, Shuhei; Miura, Katsuyuki.

In: Journal of Pharmacological Sciences, Vol. 136, No. 1, 01.01.2018, p. 31-38.

Research output: Contribution to journalArticle

Kabei, Kazuya ; Tateishi, Yu ; Nozaki, Masakazu ; Tanaka, Masako ; Shiota, Masayuki ; Osada-Oka, Mayuko ; Nishide, Shunji ; Uchida, Junji ; Nakatani, Tatsuya ; Tomita, Shuhei ; Miura, Katsuyuki. / Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney : Special references to HIF-1 dependent gene expression of profibrogenic molecules. In: Journal of Pharmacological Sciences. 2018 ; Vol. 136, No. 1. pp. 31-38.
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