マトリセルラータンパク質(Matricellular proteins)の機能 : トロンボスポンジンを中心として
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概要
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Matricellular proteins, components of the extracellular matrix (ECM) with no directly structural roles in the ECM, are expressed primarily during development and response to injury, but not abundant in the normal adults, except in tissues with continued turnover, such as bone. Members of this class including osteonectin, thrombospondin 1 (TSP1), thrombospondin 2 (TSP2), osteopontin, and tenascin-C serve as biological mediators of cell function by interacting directly with cells or by modulating the activity of growth factors, cytokines, proteases, and other extracellular macromolecules. In addition, matricellular proteins mediate cellular de-adhesion, which refers to a reversal of the adhesive process involving the transition from a strongly adherent state with focal adhesions and stress fibers to an intermediate state of adherence. The proteins stimulate reorganization of actin stress fibers and disassembly of focal adhesion complexes but maintain a spread cell shape, while employing each unique array of signaling. The adhesive state undergoes modulation in tissue remodeling during morphogenesis and wound healing, cellular metaplasia and proliferation, and tumor metastasis. Although matricellular protein-null mice are apparently normal possibly due to redundancy of these proteins, on more careful scrutiny they display some abnormalities in collagen fibril assembly, vascular morphology or density, and connective tissue organization that are often magnified under pathological conditions. In this review, TSP1 and TSP2 showing differential spatiotemporal expression in the developing skeleton will be mainly discussed in the context of mineralizing cell biology. TSP1 accumulates in both predentin and osteoid between mineralized and unmineralized tissues, whereas TSP2 acts an autocrine inhibitor of marrow stromal cell proliferation. In particular, it is clear that high levels of TSP1 inhibit pathophysiological mineralization and contribute to calcified tissue homeostasis in response to aging and remodeling as an interface molecule.
- 徳島大学の論文
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- マトリセルラータンパク質(Matricellular proteins)の機能 : トロンボスポンジンを中心として