Locally Acting Factors in Mouse Models of Wound Healing and Papilloma Formation in Skin

Toini Pemmari

    Tutkimustuotos: VäitöskirjaCollection of Articles

    Abstrakti

    Skin covers the human body almost completely and is thus exposed to environmental hazards. This dissertation studies skin wounds and premalignant lesions of cutaneous squamous cell cancer. The body has mechanisms to combat both, but the mechanisms are imperfect. Premalignant lesions tend to progress, and scars have weaker mechanical characteristics than unwounded skin.
    Many current treatments for skin problems are locally applied since skin is easily accessible. Despite the clear advantages, such as the avoidance of systemic side effects, local treatments have disadvantages like uneven distribution in the skin.

    This dissertation has two main purposes: Firstly, to develop new, locally acting therapeutics to improve wound healing. Secondly, to understand better the mechanisms behind the development of premalignant lesions of cutaneous squamous cell carcinoma. The results of the study are available in four publications. The first publication demonstrates that carbonic anhydrase VI does not accelerate skin wound healing. The second publication shows that removing the last amino acid from the end of a skin wound-homing peptide, CRK, creates a new peptide with homing and penetration ability to skin wounds and unwounded skin. A recombinant protein containing this new peptide, tCRK, and a protein called decorin uses neuropilin-1-mediated pathway to enter cells.

    The third and fourth publication concentrate on a two-stage carcinogenesis model that can be used to study the premalignant lesions of cutaneous squamous cell carcinoma. The method is described in detail on the third publication. In the fourth publication, the two-stage carcinogenesis model is used to study the signaling of interleukins 4 and 13. Fourth publication shows that interleukin-13 receptor chain alpha 1 deficiency increases the premalignant lesion formation.

    Based on the results of the dissertation, carbonic anhydrase VI is unlikely to become a skin therapeutic in the future. However, further development of tCRK­ peptide is encouraged. The results also raise a question of the safety of long-term usage of therapeutics blocking interleukin-4 and intetleukin-13 signaling. As the results of the dissertation have been obtained from mouse models, further research and epidemiological follow-up are needed to see if the same phenomena exist in humans.
    AlkuperäiskieliEnglanti
    JulkaisupaikkaTampere
    ISBN (elektroninen)978-952-03-2475-9
    TilaJulkaistu - 2022
    OKM-julkaisutyyppiG5 Artikkeliväitöskirja

    Julkaisusarja

    NimiTampere University Dissertations - Tampereen yliopiston väitöskirjat
    Vuosikerta632
    ISSN (painettu)2489-9860
    ISSN (elektroninen)2490-0028

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