Integrin shedding as a mechanism of cellular adaptation during cardiac growth.
Integrin-mediated cell-extracellular matrix (ECM) interactions are essential for multiple cellular processes; however, little is known regarding integrin turnover during these events. Recent studies have demonstrated shedding of cell surface molecules and suggested this as a potential mechanism for integrin turnover. Confocal microscopy of mouse hearts under different physiological conditions demonstrated the presence of beta(1)-integrin-immunoreactive material in the interstitium. Culture media from neonatal rat cardiac myocytes and fibroblasts contained a 55-kDa fragment of beta(1)-integrin. Attachment to ECM components, response to phorbol 12-myristate 13-acetate stimulation, and matrix metalloproteinase inhibition assays demonstrated that fibroblasts responded differently to the fragment compared with myocytes. The beta(1)-integrin fragment stimulated myocyte attachment to collagen and the fragment itself bound a variety of ECM proteins. These studies indicate that as myocytes and fibroblasts change size and shape, cellular contacts with the ECM are altered, resulting in the liberation of a beta(1)-integrin fragment from the cell surface. Integrin shedding may represent a novel mechanism of rapidly modifying cell-ECM contacts during various cellular processes.
Goldsmith
Edie C
EC
Department of Developmental Biology and Anatomy, University of South Carolina School of Medicine, Columbia 29208, USA. ediegold@med.sc.edu
Carver
Wayne
W
McFadden
Alex
A
Goldsmith
Jack G
JG
Price
Robert L
RL
Sussman
Mark
M
Lorell
Beverly H
BH
Cooper
Garth
G
Borg
Thomas K
TK
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002448:Cell Adhesion / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology; D006321:Heart / Q000254:growth & development* / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D019012:Integrin beta1 / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology*; D010703:Phorbol Esters / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats
D019012:Integrin beta1; D061965:Matrix Metalloproteinase Inhibitors; D010703:Phorbol Esters; D011480:Protease Inhibitors; D003094:Collagen