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Title page for ETD etd-07012014-111709


Type of Document Dissertation
Author Almodóvar García, Karinna
URN etd-07012014-111709
Title Ankrd1, a Modulator of Matrix Metabolism and Cell-Matrix Interactions
Degree PhD
Department Pathology
Advisory Committee
Advisor Name Title
Pampee P. Young Committee Chair
Alissa M. Weaver Committee Member
David M. Bader Committee Member
Jeffrey M. Davidson Committee Member
Linda J. Sealy Committee Member
Keywords
  • Ankrd1
  • cell contraction
  • transcription factors
  • CARP
  • wound healing
  • fibroblasts
  • matrix metalloproteinases
  • gene regulation
  • human burn wounds
  • gene expression
  • matrix remodeling
  • integrins
Date of Defense 2014-06-24
Availability unrestricted
Abstract
Normal tissue repair involves a series of highly coordinated events that include inflammation, granulation tissue formation, revascularization, and tissue remodeling. The transcriptional co-factor, ankyrin repeat domain protein 1 (Ankrd1), is rapidly and highly up regulated by wounding and tissue injury in mouse skin. Ankrd1 is also strongly elevated in human wounds. Overexpression of Ankrd1 in wounds by adenoviral gene transfer enhances wound healing. Ankrd1 has dual roles: a transcriptional co-regulator of several genes and a structural component of the sarcomere, where it forms a multi-component complex with the giant elastic protein, titin. Deletion of Ankrd1 results in a wound healing phenotype characterized by impaired wound closure and reduced granulation tissue thickness. In vitro studies confirmed the importance of Ankrd1 for proper cell-matrix interaction. We identified two Ankrd1-target genes, Collagenase-3 (MMP-13) and Stromelysin-2 (MMP-10). Both, MMP-13 and MMP-10 are important players in matrix turnover during physiological and pathological events. In summary, Ankrd1 regulates genes involve in remodeling of the extracellular matrix and is essential for proper interaction with the extracellular matrix in vitro.
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