A distinctive distribution of hypoxia-inducible factor-1α in cultured renal tubular cells with hypoperfusion simulated by coverslip placement

Tomoko Honda, Yosuke Hirakawa, Kiichi Mizukami, Toshitada Yoshihara, Tetsuhiro Tanaka, Seiji Tobita, Masaomi Nangaku

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Chronic hypoxia in the renal tubulointerstitium plays a key role in the progression of chronic kidney disease (CKD). It is therefore important to investigate tubular hypoxia and the activity of hypoxia-inducible factor (HIF)-1α in response to hypoxia. Rarefaction of the peritubular capillary causes hypoperfusion in CKD; however, the effect of hypoperfusion on HIFs has rarely been investigated. We induced hypoperfusion caused by coverslip placement in human kidney-2 cells, and observed an oxygen gradient under the coverslip. Immunocytochemistry of HIF-1α showed a doughnut-shaped formation on the edge of a pimonidazole-positive area, which we named the “HIF-ring”. The oxygen tension of the HIF-ring was estimated to be between approximately 4 mmHg and 20 mmHg. This result was not compatible with those of past research showing HIF-1α accumulation in the anoxic range with homogeneous oxygen tension. We further observed the presence of a pH gradient under a coverslip, as well as a shift of the HIF ring due to changes in the pH of the culture medium, suggesting that the HIF ring was formed by suppression of HIF-1α related to low pH. This research demonstrated that HIF-1α activation mimics the physiological state in cultured cells with hypoperfusion.

Original languageEnglish
Article numbere14689
JournalPhysiological Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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