Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling.
It is presently accepted that fibroblast/myofibroblast modulation represents a crucial step in granulation tissue contraction and in the production of the connective tissue deformations typical of fibrocontractive diseases. In addition to synthesizing extracellular matrix (ECM) components, myofibroblasts can develop tensile force through the neoformation of alpha-smooth muscle actin (alpha-SMA) containing cytoplasmic stress fibers. Tension has been shown to be a crucial regulator of connective tissue remodeling. In order to coordinate tension distribution within connective tissue, cell-matrix and cell-cell contacts appear essential. This review addresses the formation, molecular structure and function of such structures that are characterized by their association with intracytoplasmic actin filaments. Actin associated cell-matrix adhesions appear to provide the interface between ECM components and intracellular stress fibers, thus contributing to the transmission of force to the substrate and to the detection of stress level in the matrix. Cell-cell adherens junctions appear to synchronize myofibroblast contractile activity. Further studies investigating the functions of these structures will be important for the understanding of the mechanisms of granulation tissue evolution and for the planification of strategies in view of influencing connective tissue deformations.
Hinz
Boris
B
Laboratory of Cell Biophysics, Swiss Federal Institute of Technology, Bâtiment SG-AA-B 143, CH-1015 Lausanne, Switzerland. boris.hinz@epfl.ch
Gabbiani
Giulio
G
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D021982:Cell-Matrix Junctions / Q000502:physiology*; D003238:Connective Tissue / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D032342:Muscle Cells / Q000166:cytology; D022502:Stress Fibers / Q000502:physiology; D014945:Wound Healing
D000199:Actins