Abstract

The long term goal of this research project is to increase our understanding of the wound contraction process. A better understanding of contraction is an essential step in the search for therapeutic strategies necessary to control contraction and scarring. Towards this goal, we have been studying several variations of an in vitro model of wound contraction. During the next five years, we plan an integrated approach in which we will use the in vitro wound contraction model to study cell signaling, regulation of contraction, and apoptosis.
Specific Aim #1 focuses on the mitogen-activated protein kinase signal transduction pathways activated by stressed matrix contraction, autocrine regulation, and immediate early gene transcription.
Specific Aim #2 focuses on the mechanisms responsible for stimulation of stressed and floating collagen contraction by platelet-derived growth factor and lysophosphatidic acid, differences in the regulation of floating and stressed matrix contraction, and the role of mechanical stress in myofibroblast differentiation.
Specific Aim #3 focuses on the factors that contribute to apoptosis of cells undergoing stressed matrix contraction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM031321-24
Application #
7152515
Study Section
Special Emphasis Panel (NSS)
Program Officer
Ikeda, Richard A
Project Start
1983-12-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
24
Fiscal Year
2007
Total Cost
$443,700
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

da Rocha-Azevedo, Bruno; Ho, Chin-Han; Grinnell, Frederick (2015) PDGF?stimulated dispersal of cell clusters and disruption of fibronectin matrix on three-dimensional collagen matrices requires matrix metalloproteinase-2. Mol Biol Cell 26:1098-105
Liu, Zhenan; Ho, Chin-Han; Grinnell, Frederick (2014) The different roles of myosin IIA and myosin IIB in contraction of 3D collagen matrices by human fibroblasts. Exp Cell Res 326:295-306
Velasquez, Lissette S; Sutherland, Lillian B; Liu, Zhenan et al. (2013) Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing. Proc Natl Acad Sci U S A 110:16850-5
da Rocha-Azevedo, Bruno; Grinnell, Frederick (2013) Fibroblast morphogenesis on 3D collagen matrices: the balance between cell clustering and cell migration. Exp Cell Res 319:2440-6
Grinnell, Frederick; Ho, Chin-Han (2013) The effect of growth factor environment on fibroblast morphological response to substrate stiffness. Biomaterials 34:965-74
da Rocha-Azevedo, Bruno; Ho, Chin-Han; Grinnell, Frederick (2013) Fibroblast cluster formation on 3D collagen matrices requires cell contraction dependent fibronectin matrix organization. Exp Cell Res 319:546-55
Rhee, Sangmyung; Ho, Chin-Han; Grinnell, Frederick (2010) Promigratory and procontractile growth factor environments differentially regulate cell morphogenesis. Exp Cell Res 316:232-44
Grinnell, Frederick; Petroll, W Matthew (2010) Cell motility and mechanics in three-dimensional collagen matrices. Annu Rev Cell Dev Biol 26:335-61
Miron-Mendoza, Miguel; Seemann, Joachim; Grinnell, Frederick (2010) The differential regulation of cell motile activity through matrix stiffness and porosity in three dimensional collagen matrices. Biomaterials 31:6425-35
Jiang, Hongmei; Rhee, Sangmyung; Ho, Chin-Han et al. (2008) Distinguishing fibroblast promigratory and procontractile growth factor environments in 3-D collagen matrices. FASEB J 22:2151-60

Showing the most recent 10 out of 68 publications