Mechanosensitive induction of apoptosis in fibroblasts is regulated by thrombospondin-1 and integrin associated protein (CD47).
Fibroblasts are cultured in three-dimensional collagen matrices to investigate the effect of mechanical tension on the regulation of apoptosis. Under the influence of mechanical loading, the cells show little apoptosis whereas releasing of tension leads to an increase up to tenfold during the first 24 h and remains constant for further 48 h. An autocrine loop of the integrin alpha(V)beta(3)/CD47 receptor complex and thrombospondin-1 is identified as the molecular coupling device between mechanical loading and apoptosis: The integrin alpha(V)beta(3) is expressed under mechanical loading as well as unloading whereas the CD47 could only be identified after the release of tension. The secreted thrombospondin binds to the active receptor and induces apoptosis. The presented mechanosensitive regulation of apoptosis in fibroblast cultures could be an essential mechanism for the regression of the granulation tissue by apoptosis in the process of wound healing.
Graf
R
R
Institute of Biochemistry, Technical University of Darmstadt, Petersenstrasse 22, D-64287 Darmstadt, Germany.
Freyberg
M
M
Kaiser
D
D
Friedl
P
P
D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D003094:Collagen; D003470:Culture Media; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000502:physiology; D008954:Models, Biological; D013314:Stress, Mechanical; D019700:Thrombospondin 1 / Q000502:physiology*; D014945:Wound Healing / Q000276:immunology / Q000502:physiology
D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D003470:Culture Media; D039302:Integrin alphaVbeta3; D019700:Thrombospondin 1; D003094:Collagen