TY - JOUR
T1 - Hypoxia and expression of hypoxia-inducible factor in the aging kidney
AU - Tanaka, Tetsuhiro
AU - Kato, Hideki
AU - Kojima, Ichiro
AU - Ohse, Takamoto
AU - Son, Daisuke
AU - Tawakami, Takahisa
AU - Yatagawa, Toshiya
AU - Inagi, Reiko
AU - Fujita, Toshiro
AU - Nangaku, Masaomi
N1 - Funding Information:
ACKNOWLEDGMENT We acknowledge Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17390246).
PY - 2006/8
Y1 - 2006/8
N2 - 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.
AB - 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.
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U2 - 10.1093/gerona/61.8.795
DO - 10.1093/gerona/61.8.795
M3 - Article
C2 - 16912095
AN - SCOPUS:33747462156
SN - 1079-5006
VL - 61
SP - 795
EP - 805
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 8
ER -