ORCID

https://orcid.org/0000-0002-8907-7439

Date of Award

Summer 8-15-2016

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Hypoxic injury to the heart causes cardiac fibrosis leading to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor which has been implicated in fibrosis following organ injury. To investigate the role of SNAIL1 in cardiac fibrosis, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 is expressed in the infarcted myocardium, especially in the myofibroblasts. Utilizing cardiac fibroblasts in-vitro we demonstrate that pro-fibrotic factors and collagen increases SNAIL1 in cardiac fibroblasts. By knocking out SNAIL1 in cardiac fibroblasts in-vitro, we demonstrate that SNAIL1 is required for adoption of myofibroblast fate, collagen 1 expression and fibrotic genes expression. Taken together the data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after injury which causes adoption of a myofibroblast phenotype and a fibrotic scar formation. The collagen deposition in the scar can maintain the elevated SNAIL1 expression in the myofibroblasts and help to propagate fibrosis.

Language

English (en)

Chair and Committee

Gregory D. Longmore

Committee Members

Robert Mecham, Kendall Blumer, Stacey Rentschler, Jeffrey Miner, David Ornitz

Comments

Permanent URL: https://doi.org/doi:10.7936/K73B5XJV

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