Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure

摘要

The loss of TGF ss or its downstream mediator, Smad3, key players in tissue repair, accelerates closure of incisional wounds in mice. In contrast, we now report that excisional ear wounds in mice lacking Smad3 enlarge compared with wild-type controls resulting from changes in extracellular matrix molecules, which alter the mech-anotransduction properties of these wounds. Specifically, levels of elastin and glycosoaminoglycans are increased, collagen fibers are more compactly organized, and matrix modulators like integrins, TGF ss 1, and matrix metalloproteinases (MMPs) are altered both basally and after wounding in Smad3 knockout mice. Mechanical testing of dorsal skin correlates these changes in matrix composition with functional parameters, specifically an increased elastic modulus, suggesting an imbalance of tissue forces. We propose that the altered mechanical elastic properties translate into a persistent retractile force that is opposed by decreased wound contractile forces contributing to the enlarging ear wound in Smad3 knockout mice. These studies highlight a previously unde-scribed role for Smad3 in the mechanotransduction of matrix unsupported ear wound closure.