Date of Award


Degree Type


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


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.