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      Myofibroblasts and mechano-regulation of connective tissue remodelling

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          Abstract

          During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.

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          Most cited references130

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          Transforming growth factor beta in tissue fibrosis.

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            Pericyte loss and microaneurysm formation in PDGF-B-deficient mice.

            Platelet-derived growth factor (PDGF)-B-deficient mouse embryos were found to lack microvascular pericytes, which normally form part of the capillary wall, and they developed numerous capillary microaneurysms that ruptured at late gestation. Endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells. Pericytes may contribute to the mechanical stability of the capillary wall. Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts.
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              Transmembrane crosstalk between the extracellular matrix--cytoskeleton crosstalk.

              Integrin-mediated cell adhesions provide dynamic, bidirectional links between the extracellular matrix and the cytoskeleton. Besides having central roles in cell migration and morphogenesis, focal adhesions and related structures convey information across the cell membrane, to regulate extracellular-matrix assembly, cell proliferation, differentiation, and death. This review describes integrin functions, mechanosensors, molecular switches and signal-transduction pathways activated and integrated by adhesion, with a unifying theme being the importance of local physical forces.
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                Author and article information

                Journal
                Nature Reviews Molecular Cell Biology
                Nat Rev Mol Cell Biol
                Springer Science and Business Media LLC
                1471-0072
                1471-0080
                May 2002
                May 2002
                : 3
                : 5
                : 349-363
                Article
                10.1038/nrm809
                11988769
                35caaac1-b0ef-4bea-9d6b-1ad270142284
                © 2002

                http://www.springer.com/tdm


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