**4.13. HOXD10**

*HOXD10* is another negative regulator gene for angiogenesis as its overexpression inhibited dermal microvascular endothelial cell migration in vitro [53]. In addition, it has been shown that HoxD10 reduces the expression of GATA-binding protein transcription factor, a family of transcription factors that contain two zinc finger motifs and bind to the DNA sequence (A/T) GATA(A/G), from where it acquires its name. HoxD10 via those transcription factors is able to regulate expression of VEGFR1 and VEGFR2 in differentiated endothelial cells [83]. Therefore,

**Figure 3.** HOX genes regulate angiogenesis. Differential expression of Hox genes tightly regulates endothelial cell proliferation, migration, adhesion, and blood vessel formation (angiogenesis) by activating or silencing relevant target genes, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), platelet factor 4 (PF4) or chemokine (C-X-C motif) ligand 4 (CXCL4), interleukin-8 (IL-8), integrin beta 1 (ITGβ1), and both vascular endothelial growth factor receptors 1 and 2 (VEGFR1/VEGFR2).

these observations suggest that there is an overlapping and complementary role between Hox genes to maintain a balance between pro-angiogenic and anti-angiogenic states (**Figure 3**).
