This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Wound healing is a process that involves multiple stages, each having different cells and soluble factors modulating the process. Both keratinocytes and fibroblasts become activated during the process, the former primarily involved in reestablishing the barrier, while the latter is involved with contraction and matrix deposition. Many studies have described events involving either the fibroblast or the keratinocyte, but only recently have there been investigations into crosstalk between these two cell types. Such interactions are believed necessary for proper wound healing to occur. One recent study has shown that keratinocytes affect fibroblasts during TGF induction of the myofibroblast phenotype. Fibroblasts initially respond to endothelin and become contractile, then modulate into a myofibroblast days later. In addition, fibroblasts adjacent to keratinocytes differentiate the quickest. These observations indicate the importance of keratinocyte/fibroblast interactions that may be occurring during wound healing in vivo. The purpose of this study is to understand the mechanism of force transduction during keratinocyte/fibroblast interactions in vitro. This will be done by establishing a skin equivalent in vitro, a model where keratinocytes are layered atop a fibroblast-populated collagen gel to mimic skin. The skin equivalent will be tethered to a unique force transducer to measure force generated by the cells within the skin equivalent. Measurement of force generated (in the presence or absence of contraction agonists) over a period of 10 minutes to 48 hours will be collected. The ability of the cells to respond to growth factors will also be tested. Future studies will determine the role of in vitro cell age. Data collection will begin in the summer of 2005.
Showing the most recent 10 out of 165 publications
