? This supplement to NIH grant AR44518 """"""""Galvanotaxis and Wound Healing"""""""" will use DNA microarray technology to investigate the changes in gene expression induced by electric stimulation of wound healing. Electric stimulation in the form of applied electric fields is used clinically to heal bone and soft tissue wounds. It is also being used with increasing frequency now that the Centers for Medicare and Medicaid Services has approved this therapy for reimbursement for treatment of chronic skin ulcers. Yet the knowledge behind the molecular mechanisms that mediate the effectiveness of this approach is lacking. The parent grant seeks to delineate the signal transduction mechanisms by which applied DC electric fields direct migration (galvanotaxis) in human skin-derived keratinocytes. This supplement extends the scope of the parent grant to include the effects of applied DC fields on dermal as well as epidermal tissues. The strategy propose is to engineer epidermal, dermal or composite skin equivalent tissues using cultured keratinocytes and fibroblast and use these bioengineered tissues in models of wound healing. The use of bioengineered tissues confers the advantage of constraining genetic variability in the test model, allowing the changes in gene expression induced by wounding, and subsequently, by the application of DC electric fields to be more easily detected. The proposal offers a unique team of investigators including the PI who has expertise in clinical wound-healing, tissue engineering and studies the effects of electrical stimulation in skin, and co-investigator Prof. Robert Rice, a recognized expert in keratinocyte biology and director of the UC Davis DNA Microarray Facility, and co-investigator Prof. David Rocke, director of the Center for Image Processing and Integrated Computing, with unique expertise in bioinformatics and analysis of large data sets. Combining their unique expertise and resources to focus on the question of gene expression in an already operational model for modulating human skin wound healing provides powerful synergistic potential for deriving new insights into this process. This knowledge will provide the opportunity to develop novel therapeutic interventions to enhance wound repair. ? ? ?
| Sivamani, Raja K; Shi, Biao; Griffiths, Elizabeth et al. (2014) Acute wounding alters the beta2-adrenergic signaling and catecholamine synthetic pathways in keratinocytes. J Invest Dermatol 134:2258-2266 |
| Yang, Hsin-Ya; Charles, Roch-Philippe; Hummler, Edith et al. (2013) The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes. J Cell Sci 126:1942-51 |
| Pullar, Christine E; Le Provost, Gabrielle S; O'Leary, Andrew P et al. (2012) ?2AR antagonists and ?2AR gene deletion both promote skin wound repair processes. J Invest Dermatol 132:2076-84 |
| Rizzo, Amilcar Ezequiel; Beckett, Laurel A; Baier, Brian S et al. (2012) The linear excisional wound: an improved model for human ex vivo wound epithelialization studies. Skin Res Technol 18:125-32 |
| Liu, Wei; Hsu, Daniel K; Chen, Huan-Yuan et al. (2012) Galectin-3 regulates intracellular trafficking of EGFR through Alix and promotes keratinocyte migration. J Invest Dermatol 132:2828-37 |
| Steenhuis, P; Huntley, R E; Gurenko, Z et al. (2011) Adrenergic signaling in human oral keratinocytes and wound repair. J Dent Res 90:186-92 |
| Sivamani, Raja K; Schwartz, Michael P; Anseth, Kristi S et al. (2011) Keratinocyte proximity and contact can play a significant role in determining mesenchymal stem cell fate in human tissue. FASEB J 25:122-31 |
| Lulevich, Valentin; Yang, Hsin-ya; Isseroff, R Rivkah et al. (2010) Single cell mechanics of keratinocyte cells. Ultramicroscopy 110:1435-42 |
| Sivamani, Raja K; Porter, Scott M; Isseroff, R Rivkah (2009) An epinephrine-dependent mechanism for the control of UV-induced pigmentation. J Invest Dermatol 129:784-7 |
| Sivamani, Raja K; Pullar, Christine E; Manabat-Hidalgo, Catherine G et al. (2009) Stress-mediated increases in systemic and local epinephrine impair skin wound healing: potential new indication for beta blockers. PLoS Med 6:e12 |
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