This proposal outlines a strategy to elucidate the mechanism of function of Hox3-group genes during tissueremodeling in both normal healing and impaired healing using a diabetic mouse model. The proposedstudies, focused on HoxaS, extend from our previous work on the related HoxbS and HoxdS genes which actto promote angiogenesis and wound repair. Kim's work, over the past year and a half, has shown that HoxaSis a more potent factor than HoxdS in wound repair, and that some of the cellular mechanisms which underliethis characteristic include the ability of HoxaS to induce keratinocyte migration, whereas HoxdS does not. AsHoxaS appears to activate distinct target genes from HoxbS or HoxdS, Kim will investigate whether thesegenes are direct targets of HoxaS, as well as identify and characterize additional direct targets of HoxS-groupgenes during angiogenesis and wound repair using chromatin immunoprecipitation. Finally, in order to betterunderstand the cellular pathology of impaired wound repair in the diabetic environment, Kim will test whethercytokines with established roles in wound healing normally act to induce expression of HoxS-group genesand whether the wound healing functions of these cytokines are dependent on the activation of these genes.
| Restivo, Terry E; Mace, Kimberly A; Harken, Alden H et al. (2010) Application of the chemokine CXCL12 expression plasmid restores wound healing to near normal in a diabetic mouse model. J Trauma 69:392-8 |
| Mace, Kimberly A; Restivo, Terry E; Rinn, John L et al. (2009) HOXA3 modulates injury-induced mobilization and recruitment of bone marrow-derived cells. Stem Cells 27:1654-65 |
| Yu, Diana H; Mace, Kimberly A; Hansen, Scott L et al. (2007) Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-alpha protein synthesis and function during cutaneous repair in diabetic mice. Wound Repair Regen 15:628-35 |
| Mace, Kimberly A; Yu, Diana H; Paydar, Keyianoosh Z et al. (2007) Sustained expression of Hif-1alpha in the diabetic environment promotes angiogenesis and cutaneous wound repair. Wound Repair Regen 15:636-45 |
