With increasing age, the connective tissues of humans show evidence of deterioration and defective repair. Among the important alterations are (1) dermal changes; thinning of the skin, loss of collagen, fragmentation of elastic fibers, and diminished wound repair capacity and (2) blood vessel changes: thickening and stiffening of the aortic wall and decreased rates of capillary bed regeneration. We wish to address the cellular and molecular mechanisms which may lead to the deterioration or defective repair of the two principal connective tissue proteins of these organs: elastin and collagen. Although numerous morphologic and chemical studies have previously attempted to address these questions, the results have been disparate or inconclusive. Our approach will focus on collagen and elastin biosynthesis and degradation as specific, differentiated functions of dermal and vascular cells. Three experimental systems will be employed: (1) the human skin fibroblast, derived from aging donor skin, progeroid skin, and aged in vitro; (2) rat dermal cells (fibroblastic and endothelial) as they participate in an in vivo wound healing model in the aging rat and as they respond to a potent, angiogenic, growth factor; (3) rat aorta and its vascular smooth muscle cells as an aging model for the arterial wall. The differentiated parameters to be evaluated will be the rates of synthesis and degradation of elastin and several of the genetically distinct collagen types. These analyses will address specific molecular control mechanisms, such as changes in transcriptional activity of structural genes, i.e. messenger RNA levels, and absolute and relative rates of protein synthesis. In addition, these projects will identify and quantitate collagenolytic and elastolytic proteinases which may have an important role in the remodeling or degeneration of skin and blood vessels.
| Davidson, Jeffrey M; Yu, Fang; Opalenik, Susan R (2013) Splinting Strategies to Overcome Confounding Wound Contraction in Experimental Animal Models. Adv Wound Care (New Rochelle) 2:142-148 |
| Hines, Kelly M; Ashfaq, Samir; Davidson, Jeffrey M et al. (2013) Biomolecular signatures of diabetic wound healing by structural mass spectrometry. Anal Chem 85:3651-9 |
| Adolph, Elizabeth J; Hafeman, Andrea E; Davidson, Jeffrey M et al. (2012) Injectable polyurethane composite scaffolds delay wound contraction and support cellular infiltration and remodeling in rat excisional wounds. J Biomed Mater Res A 100:450-61 |
| Makowski, Alexander J; Davidson, Jeffrey M; Mahadevan-Jansen, Anita et al. (2012) In vivo analysis of laser preconditioning in incisional wound healing of wild-type and HSP70 knockout mice with Raman spectroscopy. Lasers Surg Med 44:233-44 |
| Hafeman, Andrea E; Zienkiewicz, Katarzyna J; Zachman, Angela L et al. (2011) Characterization of the degradation mechanisms of lysine-derived aliphatic poly(ester urethane) scaffolds. Biomaterials 32:419-29 |
| Schultz, Gregory S; Davidson, Jeffrey M; Kirsner, Robert S et al. (2011) Dynamic reciprocity in the wound microenvironment. Wound Repair Regen 19:134-48 |
| Hoffmann, Daniel C; Textoris, Christine; Oehme, Felix et al. (2011) Pivotal role for alpha1-antichymotrypsin in skin repair. J Biol Chem 286:28889-901 |
| Saraswati, Sarika; Alfaro, Maria P; Thorne, Curtis A et al. (2010) Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post-MI cardiac remodeling. PLoS One 5:e15521 |
| Martinez-Ferrer, Magaly; Afshar-Sherif, Ali-Reza; Uwamariya, Consolate et al. (2010) Dermal transforming growth factor-beta responsiveness mediates wound contraction and epithelial closure. Am J Pathol 176:98-107 |
| Davidson, Jeffrey M (2010) Can scarring be turned off? Am J Pathol 176:1588-91 |
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