science.editor
Posts 45
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KEY CONTENT:
Rho regulation of myosin II-dependent alpha-smooth muscle actin contraction in tissue regeneration (Simon and Simone Collins Studentship)
Dermal, musculoskeletal and vascular tissues are under continuous tissue tension, which is most evident in ruptured tendons and skin grafts that contract to 1/10th of their original size. Unmet clinical needs are to prevent tissue contraction at the time of injury and to re-establish normal tissue tension during tissue regeneration. We have shown that tendon contraction is caused by activated fibroblasts (myofibroblasts) using non-muscle myosin II motors attached to actin filaments to pull on the surrounding extracellular matrix. The cells express alpha-smooth muscle actin, which is a mechanosensitive protein that is expressed by embryonic fibroblasts and myofibroblasts at sites of tissue damage and regeneration. We have identified a Rho GTPase activating protein (GAP) that negatively regulates alpha-smooth muscle actin and are breeding knockout mice for this project. We have also shown that our GAP and -smooth muscle actin are upregulated in human mesenchymal stem cells that regenerate tendons in our 3D cell culture system. The project is to use our knockout mice and 3D cell culture system to understand the relationship between non-muscle II motors, alpha-smooth muscle actin and our newly-identified Rho GAP in tissue tension and tissue regeneration.
Dept/School Faculty of Life Sciences, University of Manchester
Project Supervisor(s) Prof K E Kadler
Original Source: http://www.findaphd.com/search/showproject.asp?projectid=28558
edited by science.editor on 6/21/2010
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