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Please use this identifier to cite or link to this item: http://hdl.handle.net/1993/3174

Title: Expression of C184M in primary cardiac myofibroblasts and its role in contractility and collagen production in NIH 3T3 fibroblasts
Authors: Nazari, Mansoreh
Supervisor: Ian Dixon (Physiology)
Examining Committee: Mary Lynn Duckworth (Physiology), Robert Shiu (Physiology), Nasrin Mesaeli(Biochemistry and Medical Genetics)
Graduation Date: October 2009
Keywords: C184M, cardiac myofibroblasts, TGF-b, collagen, NIH 3T3 cells, contractility
Issue Date: 21-Aug-2009
Abstract: Cardiac fibroblasts are capable of a phenotype shift to myofibroblasts and the latter contribute to wound healing and interstitial fibrosis. TGF-β1 signals through R-Smads and Co-Smad proteins and modulates fibrillar collagen deposition. It also influences myofibroblast cells contractility, which they confer torsional forces on the surrounding matrix. c-Ski plays an inhibitory role in TGF-β1 signaling. C184M is a 27 kDa protein that is a novel cytosolic partner of c-Ski. c-Ski-C184M complexes may negatively regulate TGF-β1 signaling via sequestering R-Smad in the cytosol, however, the role of C184M in cardiac fibrosis is unknown. Herein we characterize the expression of C184M and explore its role in TGF-β1 signaling. We found that C184M is expressed in P0 primary fibroblasts, P1 and P2 cardiac myofibroblasts and as well in NIH 3T3 cells. Western blot analysis revealed that the C184M is not responsive to TGF-β1 treatment (10ng/ml, 12, 24 and 48hr treatment) and that Smad3 overexpression does not influence expression of C184M protein in P1 cardiac myofibroblasts. In the presence of overexpressed C184M, immunofluorescence studies indicated a shift in localization of Smad3 from a diffuse cytosolic pattern to a distinctly punctuate cytosolic pattern. C184M overexpression abrogates the effects of TGF-β1 mediated increased collagen synthesis in NIH 3T3 cells. Further, C184M is involved in reduction of contractility of NIH 3T3 cells.
URI: http://hdl.handle.net/1993/3174
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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