Fig. 2.

Examples of direct transcriptional HIF targets with relevance to kidney function. Shown are selected direct HIF target genes and their classification into functional groups. For a comprehensive list of HIF target genes, the reader is referred to Wenger et al. (136). Some of the HIF targets listed here appear to be preferentially regulated by HIF-2 (e.g., VEGF and EPO). In contrast to HIF-2α, HIF-1α is expressed in most renal epithelial cells, whereas HIF-2α is mainly found in endothelial cells and renal interstitial fibroblast-like cells. HIF-1α is also expressed in papillary and inner medullary interstitial and endothelial cells but was not detected in interstitial and endothelial cells of the cortex and outer medulla (103). ANP, atrial natriuretic peptide; Bnip-3, BCL2/adenovirus E1B 19-kDa-interacting protein 3 (proapoptotic BH3 domain; only BCL-2 family member); c-Met, tyrosine kinase receptor for scatter factor/hepatocyte growth factor (SF/HGF); CXCR4, chemokine receptor 4; CTGF, connective tissue growth factor; EC, endothelial cell; ECM, extracellular matrix; eNOS, endothelial nitric oxide synthase; FLT-1, fetal liver tyrosine kinase-1 (VEGF receptor-1); IC, interstitial cell; IGFBP-1, insulin growth factor binding protein-1; iNOS, inducible nitric oxide synthase; PAI-1, plasminogen activator inhibitor-1; RTEC, renal tubular epithelial cell; TIMP-1, tissue inhibitor of metalloproteinase-1.