Date of Award

2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Ruth Borghaei, PhD

Second Advisor

Farzaneh Daghigh, PhD

Third Advisor

Michael McGuinness, PhD

Fourth Advisor

Marcus G Bell, PhD

Abstract

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 on MMP-3 mRNA expression was tested in HGF, HFF, and MG-63 cell lines. Cobalt protoporphyrin IX(CoPP) was used to induce HO-1 and Tin protoporphyrin IX(SnPP) was used to inhibit HO-1 activity. MMP-3 mRNA levels were quantified using real time PCR and normalized to GAPDH mRNA levels. Treatment of fibroblast cell cultures (HGF, HFF, MG-63) with CoPP did not result in significant changes in basal or IL-1-induced MMP-3 mRNA expression. Likewise, treatment with SnPP did not cause significant changes in MMP-3 expression. These results imply that HO-1 and its products are probably not responsible for most of the increase in MMP-3 expression seen in some HGF cell cultures in response to hemin.