Gene expression profiling in pachyonychia congenita skin

Yu An Cao, Robyn P. Hickerson, Brandon L. Seegmiller, Dmitry Grapov, Maren M. Gross, Marc R. Bessette, Brett S. Phinney, Manuel A. Flores, Tycho J. Speaker, Annaleen Vermeulen, Albert A. Bravo, Anna L. Bruckner, Leonard M. Milstone, Mary E. Schwartz, Robert H. Rice, Roger L. Kaspar (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Background: Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. Objective: To better understand PC pathogenesis. Methods: RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. Results: A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. Conclusion: Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.

    Original languageEnglish
    Pages (from-to)156-165
    Number of pages10
    JournalJournal of Dermatological Science
    Volume77
    Issue number3
    DOIs
    Publication statusPublished - Mar 2015

    Fingerprint

    Pachyonychia Congenita
    Gene Expression Profiling
    Gene expression
    Skin
    Messenger RNA
    Keratins
    Biopsy
    Tapes
    Proteins
    Peptide Hydrolases
    Mutation
    Kallikreins
    Serine Proteinase Inhibitors
    Cornified Envelope Proline-Rich Proteins
    Protease Inhibitors
    Proline
    Metabolism
    Nociception
    Genes
    RNA

    Keywords

    • Desquamation
    • Genodermatosis
    • Keratinocyte
    • Monogenic skin disorder
    • MTOR signaling pathway
    • Painful palmoplantar keratoderma

    Cite this

    Cao, Y. A., Hickerson, R. P., Seegmiller, B. L., Grapov, D., Gross, M. M., Bessette, M. R., ... Kaspar, R. L. (2015). Gene expression profiling in pachyonychia congenita skin. Journal of Dermatological Science, 77(3), 156-165. https://doi.org/10.1016/j.jdermsci.2015.01.001
    Cao, Yu An ; Hickerson, Robyn P. ; Seegmiller, Brandon L. ; Grapov, Dmitry ; Gross, Maren M. ; Bessette, Marc R. ; Phinney, Brett S. ; Flores, Manuel A. ; Speaker, Tycho J. ; Vermeulen, Annaleen ; Bravo, Albert A. ; Bruckner, Anna L. ; Milstone, Leonard M. ; Schwartz, Mary E. ; Rice, Robert H. ; Kaspar, Roger L. / Gene expression profiling in pachyonychia congenita skin. In: Journal of Dermatological Science. 2015 ; Vol. 77, No. 3. pp. 156-165.
    @article{9a04b0c9d56f455690d6bd9ad486542c,
    title = "Gene expression profiling in pachyonychia congenita skin",
    abstract = "Background: Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. Objective: To better understand PC pathogenesis. Methods: RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. Results: A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. Conclusion: Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.",
    keywords = "Desquamation, Genodermatosis, Keratinocyte, Monogenic skin disorder, MTOR signaling pathway, Painful palmoplantar keratoderma",
    author = "Cao, {Yu An} and Hickerson, {Robyn P.} and Seegmiller, {Brandon L.} and Dmitry Grapov and Gross, {Maren M.} and Bessette, {Marc R.} and Phinney, {Brett S.} and Flores, {Manuel A.} and Speaker, {Tycho J.} and Annaleen Vermeulen and Bravo, {Albert A.} and Bruckner, {Anna L.} and Milstone, {Leonard M.} and Schwartz, {Mary E.} and Rice, {Robert H.} and Kaspar, {Roger L.}",
    year = "2015",
    month = "3",
    doi = "10.1016/j.jdermsci.2015.01.001",
    language = "English",
    volume = "77",
    pages = "156--165",
    journal = "Journal of Dermatological Science",
    issn = "0923-1811",
    publisher = "Elsevier",
    number = "3",

    }

    Cao, YA, Hickerson, RP, Seegmiller, BL, Grapov, D, Gross, MM, Bessette, MR, Phinney, BS, Flores, MA, Speaker, TJ, Vermeulen, A, Bravo, AA, Bruckner, AL, Milstone, LM, Schwartz, ME, Rice, RH & Kaspar, RL 2015, 'Gene expression profiling in pachyonychia congenita skin', Journal of Dermatological Science, vol. 77, no. 3, pp. 156-165. https://doi.org/10.1016/j.jdermsci.2015.01.001

    Gene expression profiling in pachyonychia congenita skin. / Cao, Yu An; Hickerson, Robyn P.; Seegmiller, Brandon L.; Grapov, Dmitry; Gross, Maren M.; Bessette, Marc R.; Phinney, Brett S.; Flores, Manuel A.; Speaker, Tycho J.; Vermeulen, Annaleen; Bravo, Albert A.; Bruckner, Anna L.; Milstone, Leonard M.; Schwartz, Mary E.; Rice, Robert H.; Kaspar, Roger L. (Lead / Corresponding author).

    In: Journal of Dermatological Science, Vol. 77, No. 3, 03.2015, p. 156-165.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Gene expression profiling in pachyonychia congenita skin

    AU - Cao, Yu An

    AU - Hickerson, Robyn P.

    AU - Seegmiller, Brandon L.

    AU - Grapov, Dmitry

    AU - Gross, Maren M.

    AU - Bessette, Marc R.

    AU - Phinney, Brett S.

    AU - Flores, Manuel A.

    AU - Speaker, Tycho J.

    AU - Vermeulen, Annaleen

    AU - Bravo, Albert A.

    AU - Bruckner, Anna L.

    AU - Milstone, Leonard M.

    AU - Schwartz, Mary E.

    AU - Rice, Robert H.

    AU - Kaspar, Roger L.

    PY - 2015/3

    Y1 - 2015/3

    N2 - Background: Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. Objective: To better understand PC pathogenesis. Methods: RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. Results: A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. Conclusion: Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.

    AB - Background: Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. Objective: To better understand PC pathogenesis. Methods: RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. Results: A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. Conclusion: Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.

    KW - Desquamation

    KW - Genodermatosis

    KW - Keratinocyte

    KW - Monogenic skin disorder

    KW - MTOR signaling pathway

    KW - Painful palmoplantar keratoderma

    UR - http://www.scopus.com/inward/record.url?scp=84925326530&partnerID=8YFLogxK

    U2 - 10.1016/j.jdermsci.2015.01.001

    DO - 10.1016/j.jdermsci.2015.01.001

    M3 - Article

    VL - 77

    SP - 156

    EP - 165

    JO - Journal of Dermatological Science

    JF - Journal of Dermatological Science

    SN - 0923-1811

    IS - 3

    ER -