• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Matriptase in Skin: Function and Regulation

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Chen_umaryland_0373D_10312.pdf
    Size:
    10.94Mb
    Format:
    PDF
    Download
    Author
    Chen, Ya-Wen
    Advisor
    Lin, Chen-Yong
    Date
    2012
    
    Metadata
    Show full item record
    Abstract
    Epidermal differentiation is a carefully orchestrated process that leads to the formation of the critical protective barrier provided by the skin. The process of generating a functional epidermal layer requires progressive remodeling of cell morphology and tissue structure, and involves significant pericellular proteolysis that must be regulated in a precisely controlled manner. In particular, the matriptase-driven protease network plays a critical role in epidermal barrier construction as well as in the regenerative processes required for wound healing. In this dissertation, I have identified and characterized novel molecular mechanisms governing the regulation of matriptase, and cellular mechanisms by which matriptase activates its molecular targets and contributes to keratinocyte differentiation and formation of epidermal barrier. First, I identified plasminogen as a keratinocyte-selective extracellular stimulus for matriptase activation. The discovery of plasminogen as an initiating signal of the protease cascade reaffirms the theory that the matriptase-uPA-plasmin cascade is not unidirectional in the activation of its components, but it is reciprocal. In addition to HAI-1, I also revealed keratinocytes employ antithrombin as a significant endogenous protease inhibitor. The enhanced role of antithrombin in matriptase inhibition in keratinocytes reveals the regulatory adaptation in stratified epithelial cells due to the changes in tissue structure, compared to the polarized epithelial cells. With the dual inhibitory mechanisms, I further revealed that matriptase acts on its molecular targets in two different ways: a rapid activation of prostasin by cell-associated active matriptase under extremely tight control of HAI-1, and the action on several other substrates, including uPA, HGF, and syndecan-1, by secreted active matriptase that is controlled by antithrombin. Last but not least, I also demonstrated that the physiological role of matriptase in human skin likely lies in the basal and spinous keratinocytes that are involved in proliferation and early differentiation. The role of matriptase in the early stages of keratinocyte life history was further supported by the increased matriptase zymogen activation in the keratinocytes of the bulge area. By charactering the prominent regulators, downstream effectors, and the expression and activation states of matriptase in human skin, a clearer picture is emerging regarding the role of matriptase in skin biology.
    Description
    University of Maryland, Baltimore. Molecular Medicine. Ph.D. 2012
    Keyword
    HAI-1
    matriptase
    protease
    Antithrombins
    Keratinocytes
    Plasminogen
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/2141
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.