Growth control mechanisms in cutaneous wound healing are the central focus of this project. Now that in vivo studies with various exogenous growth factor shave shown a biological impact on general wound repair processes, it is timely to dissect and define signalling mechanisms of cytokines and their receptors on discrete wound healing processes such askeratinocyte proliferation, migration, recruitment of inflammatory populations and extracellular matrix proteins. EGF and EGF-like ligands, their common receptor (EGF-r tyrosinekinase), and subsequent phosphorylated substrates will be studied within unique wound healing environments. Transcription of EGF like ligands and their receptor (EGF-r) will be investigated using in situ hybridization and Northern blot analysis, protein deposition will be examined using immunohistochemical staining, and binding status will be studied with autoradiography. To define epidermal wounding responses, the EGF signalling cascade will be compared in migrating and proliferating populations of wound keratinocytes, both in vitro and in an in vivo model of superficial trauma (mouse tail tape stripping). Deeper wound environments (excisional porcine wounds, human burns, human chronic wounds) will be utilized to define and contrast cytokine mechanisms which control the extracellular matrix proteins. In addition, the balance between stimulatory cytokines(EGF) and inhibitory cytokines (TGFB superfamily-BMP4) will be examined using a BMP4 transgenic mouse wound model. Lastly, exogenously applied molecules relevant to the EGF signalling cascade will be used as experimental tools to modify epidermal and/or mesenchymal components of wound repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM040437-06
Application #
3297952
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-07-01
Project End
1997-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Caldwell, Robert L; Opalenik, Susan R; Davidson, Jeffrey M et al. (2008) Tissue profiling MALDI mass spectrometry reveals prominent calcium-binding proteins in the proteome of regenerative MRL mouse wounds. Wound Repair Regen 16:442-9
Nanney, Lillian B; Woodrell, Christopher D; Greives, Mathew R et al. (2008) Calreticulin enhances porcine wound repair by diverse biological effects. Am J Pathol 173:610-30
Pollins, Alonda C; Friedman, David B; Nanney, Lillian B (2007) Proteomic investigation of human burn wounds by 2D-difference gel electrophoresis and mass spectrometry. J Surg Res 142:143-52
Caldwell, Robert L; Opalenik, Susan R; Davidson, Jeffrey M et al. (2007) Tissue profiling MALDI mass spectrometry reveals prominent calcium-binding proteins in the proteome of regenerative MRL mouse wounds. Wound Repair Regen :
Okwueze, Martina I; Cardwell, Nancy L; Pollins, Alonda C et al. (2007) Modulation of porcine wound repair with a transfected ErbB3 gene and relevant EGF-like ligands. J Invest Dermatol 127:1030-41
Ajmal, Nadeem; Riordan, Colin L; Cardwell, Nancy et al. (2003) Chemically assisted capsulectomy in the rabbit model: a new approach. Plast Reconstr Surg 112:1449-54; discussion 1462-3
Draper, Bradley K; Komurasaki, Toshi; Davidson, Mari K et al. (2003) Topical epiregulin enhances repair of murine excisional wounds. Wound Repair Regen 11:188-97
Ajmal, Nadeem; Riordan, Colin L; Cardwell, Nancy et al. (2003) The effectiveness of sodium 2-mercaptoethane sulfonate (mesna) in reducing capsular formation around implants in a rabbit model. Plast Reconstr Surg 112:1455-61; discussion 1462-3
Milatovic, Snjezana; Nanney, Lillian B; Yu, Yingchun et al. (2003) Impaired healing of nitrogen mustard wounds in CXCR2 null mice. Wound Repair Regen 11:213-9

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