Date of Award

8-16-2024

Document Type

Open Access Thesis

Department

Biomedical Science

First Advisor

Holly LaVoie

Abstract

The main protein component of extracellular matrix is collagen, which fills spaces and supports cells. In the heart, collagen provides the scaffolding for cardiomyocytes and aids in contractile forces. In the ovary, collagen gives follicles their structural support. MMP14 or membrane type 1 matrix metalloproteinase is a membrane bound proteinase that cleaves extracellular matrix proteins, including collagen I and III. Recent studies have shown that overexpression of MMP14 influences collagen content in the heart, and elevated MMP14 has also been linked to ovarian cancer. In the current study, we investigate the effects of overexpression of a human MMP14 (hMMP14) transgene in fibroblasts on the levels of collagen in heart and ovarian tissue and cardiomyocyte size. hMMP14 transgenic and FVB/NJ wildtype mice at pregnancy day 17 (ed17), postpartum day 49 (ppd49) or as age-matched virgins were used in this study. Ovarian and heart tissues were stained with Picrosirius red (PSR) and Masson’s trichrome stain. Cardiomyocyte cross-sectional area and PSR-detected collagen content were quantified using Image J. Our results showed that hMMP14 transgene expression did affect combined collagen I and III abundance as measured by PSR quantification in ovaries compared to wildtypes, but collagen content was not affected by reproductive status. Combined collagen I and III abundance in left ventricles did not vary by genotype or with reproductive status. Cardiomyocyte cross-sectional area was also not affected by genotype or reproductive status. In summary, our microscopic analyses did not identify cardiac alterations in MMP14 transgenic mice but did reveal significant differences in ovarian collagen content between genotypes. This data will need to be combined with other biochemical analyses of collagen I and III in future studies to gain a better understanding of the impact of excess hMMP14 on ovarian and cardiac structure.

Rights

© 2024, Emily Catherine Walliser

Available for download on Saturday, May 31, 2025

Included in

Biology Commons

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