Hypoxia and expression of hypoxia-inducible factor in the aging kidney

Tetsuhiro Tanaka, Hideki Kato, Ichiro Kojima, Takamoto Ohse, Daisuke Son, Takahisa Tawakami, Toshiya Yatagawa, Reiko Inagi, Toshiro Fujita, Masaomi Nangaku

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)


Renal senescence is characterized by interstitial fibrosis and loss of peritubular capillaries. In this study, we provided evidence of tubulointerstitial hypoxia and the operation of hypoxia-inducible factor (HIF) in the aging kidney. Using two distinct methods, pimonidazole immunostaining and the expression of the "hypoxia-responsive" reporter of the transgenic rats, we identified the age-related expansion of hypoxia in all areas of the kidney. Expansion was most prominent in the cortex. Clusters of hypoxic tubules were observed in the superficial cortical zones, areas adjacent to the outer nephrons and expanded in the medullary rays. The degree of hypoxia was positively correlated with the age-related tubulointerstitial injury (R 2 = 0.88, p < .01), which was associated with the upregulation of HIF-regulated genes, such as vascular endothelial growth factor (VEGF) and glucose transporter-1 (GLUT1) (real-time polymerase chain reaction). These findings point to the involvement of hypoxia and highlight the pathological relevance of HIF and its target genes in the aging kidney.

Original languageEnglish
Pages (from-to)795-805
Number of pages11
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number8
Publication statusPublished - 2006 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology


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