Cand.med. Ole Jørgen Kaasbøll at Institute of Clinical Medicine will be defending the thesis “Studies of the structure-activity relationships, signaling properties and functions of Connective Tissue Growth Factor” for the degree of PhD (Philosophiae Doctor).
Trial Lecture - time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Roel Goldschmeding, Department of Pathology, University Medical Center Utrecht, The Netherlands
- Second opponent: Professor Brahim Chaqour, State University of New York (SUNY), Downstate Medical Center, USA
- Third member and chair of the evaluation committee: Professor Kåre-Olav Stensløkken, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Finn Olav Levy, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor II Håvard Attramadal, Faculty of Medicine, University of Oslo
Summary
The work presented and discussed in this thesis relates to the protein known as Connective Tissue Growth Factor (also known as CCN2). Connective Tissue Growth Factor is a secreted protein that is highly expressed in settings of chronic heart disease. In this work we demonstrate the cardioprotective capacity of recombinant Connective Tissue Growth Factor when administered after ischemia in an isolated mouse heart system. Furthermore we demonstrated that recombinant Connective Tissue Growth Factor could directly target primary cardiac fibroblasts and stimulate a type of cell cycle arrest known as senescence in the primary cardiac fibroblasts. We also produced and purified several variants of recombinant Connective Tissue Growth Factor, investigated the relationship between the proteolytic processing of Connective Tissue Growth Factor and its biologic activity, and surprisingly found that proteolytic processing is necessary to release the latent activity of unprocessed Connective Tissue Growth Factor. Thus, we conclude that Connective Tissue Growth Factor is in fact a preproprotein, and that the carboxyl-terminal domains III and IV constitute the active, mature form of Connective Tissue Growth Factor.
Additional information
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