Transcriptional profiling of rapamycin-treated fibroblasts from hypertrophic and keloid scars

Victor W. Wong, Fanglei You, Michael Januszyk, Geoffrey C. Gurtner, Anna Kuang

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Excess scar formation after cutaneous injury can result in hypertrophic scar (HTS) or keloid formation. Modern strategies to treat pathologic scarring represent nontargeted approaches that produce suboptimal results. Mammalian target of rapamycin (mTOR), a central mediator of inflammation, has been proposed as a novel target to block fibroproliferation. To examine its mechanism of action, we performed genomewide microarray on human fibroblasts (from normal skin, HTS, and keloid scars) treated with the mTOR inhibitor, rapamycin. Hypertrophic scar and keloid fibroblasts demonstrated overexpression of collagen I and III that was effectively abrogated with rapamycin. Blockade of mTOR specifically impaired fibroblast expression of the collagen biosynthesis genes PLOD, PCOLCE, and P4HA, targets significantly overexpressed in HTS and keloid scars. These data suggest that pathologic scarring can be abrogated via modulation of mTOR pathways in procollagen and collagen processing.

    Original languageEnglish (US)
    Pages (from-to)711-719
    Number of pages9
    JournalAnnals of Plastic Surgery
    Volume72
    Issue numberSUPPL. 2
    DOIs
    StatePublished - 2014

    Fingerprint

    Hypertrophic Cicatrix
    Keloid
    Sirolimus
    Fibroblasts
    Cicatrix
    Collagen
    Procollagen
    Inflammation Mediators
    Skin
    Wounds and Injuries
    Genes

    Keywords

    • Collagen
    • Fibroblast
    • Hypertrophic scar
    • Keloid
    • Microarray

    ASJC Scopus subject areas

    • Surgery
    • Medicine(all)

    Cite this

    Transcriptional profiling of rapamycin-treated fibroblasts from hypertrophic and keloid scars. / Wong, Victor W.; You, Fanglei; Januszyk, Michael; Gurtner, Geoffrey C.; Kuang, Anna.

    In: Annals of Plastic Surgery, Vol. 72, No. SUPPL. 2, 2014, p. 711-719.

    Research output: Contribution to journalArticle

    Wong, Victor W. ; You, Fanglei ; Januszyk, Michael ; Gurtner, Geoffrey C. ; Kuang, Anna. / Transcriptional profiling of rapamycin-treated fibroblasts from hypertrophic and keloid scars. In: Annals of Plastic Surgery. 2014 ; Vol. 72, No. SUPPL. 2. pp. 711-719.
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