Abstract
Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling.
Highlights
Living tissue is composed of cells and extracellular matrix (ECM)
In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain the tissue structure by supporting the shape and position of cells, integrating and transmitting mechanical forces generated inside the cells to whole tissue
Tenascin-C (TNC) is a non-structural ECM protein highly expressed in morphogenesis and tissue remodeling, and has a wide range of effects on cell responses
Summary
Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain the tissue structure by supporting the shape and position of cells, integrating and transmitting mechanical forces generated inside the cells to whole tissue. ECM is important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Tenascin-C (TNC) is a non-structural ECM protein highly expressed in morphogenesis and tissue remodeling, and has a wide range of effects on cell responses. Emerging evidence suggests that TNC may be involved in mechanotransduction in response to mechanical stress. We will focus on the adaptive role of TNC in the mechanical stress response in the development and pathological state of the cardiovascular system
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