Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. A. Leask

Abstract

In fibroblasts, transforming growth factor β-1 (TGFβ1) signals via canonical and non-canonical pathways to promote wound healing or hyper-contractile responses resulting in scars. The oral cavity however does not scar and fibrotic responses such as gingival hyperplasia are characterized by a hyper-proliferative response. The involvement of non-canonical, TGFβ-activated kinase-1 (TAK1) - mediated TGFβ1 signaling in gingival fibroblasts has not been previously examined. Here I show that TAK1 selective inhibitor (5Z)-7-Oxozeaenol blocks TGFβ1-induced expression of wound healing and fibrotic marker CCN2 (connective tissue growth factor) in gingival fibroblasts. Genome-wide expression profiling revealed that essentially all TGFβ1 induced genes were in fact sensitive to TAK1 inhibition in gingival fibroblasts (139/147) including those involved in proliferative and wound healing responses. This data was confirmed using RT-qPCR to detect mRNA expression as well as functional cell proliferation assay. (5Z)-7-Oxozeaenol might be investigated in the treatment of gingival hyperplasia in the future.


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