Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition
J. Clin. Invest. Debra F. Higgins, et al. 117:3810 doi:10.1172/JCI30487 [Go to this article.]

Figure 4
UUO kidneys are hypoxic prior to development of tubulointerstitial fibrosis. (A) Hypoxyprobe (Chemicon) was used to detect hypoxic regions in obstructed kidneys (UUO) 1 day and 8 days after ligation of the ureter (upper 4 panels). In contrast, hypoxyprobe staining was not detected in contralateral kidneys (CTL) 1 day after ligation but was apparent at low levels by day 8; original magnification ×200. Lower panels show cortical immunostaining for Hif-1α and Hif-2α in 8-day UUO and CTL kidneys; original magnification, ×400; arrows indicate cells with positive nuclear staining. (B) Quantitative real-time PCR analysis for Mdr-1, Pai-1, Lox, LoxL2, Collagen 1α1, and Collagen 18α1 in cortex of Hif1a^+/+ CTL and UUO kidneys 8 days after ligation. Shown are relative expression values normalized to 18S rRNA. Data points represent individual kidneys; red bars represent mean values; n = 7; *P < 0.05, **P < 0.01, ^#P < 0.001.