Gene expression profiling in pachyonychia congenita skin

被引：29

作者：

Cao, Yu-An ^{[1
]}

Hickerson, Robyn P. ^{[1
]}

Seegmiller, Brandon L. ^{[1
]}

Grapov, Dmitry ^{[2
]}

Gross, Maren M. ^{[3
]}

Bessette, Marc R. ^{[3
]}

Phinney, Brett S. ^{[2
]}

Flores, Manuel A. ^{[1
]}

Speaker, Tycho J. ^{[1
]}

Vermeulen, Annaleen ^{[3
]}

Bravo, Albert A. ^{[4
]}

Bruckner, Anna L. ^{[5
]}

Milstone, Leonard M. ^{[6
]}

Schwartz, Mary E. ^{[7
]}

Rice, Robert H. ^{[2
]}

Kaspar, Roger L. ^{[1
]}

机构：

[1] TransDerrn Inc, Santa Cruz, CA 95060 USA

[2] Univ Calif Davis, Davis, CA 95616 USA

[3] Dharmacon Part GE Healthcare, Lafayette, CO 80026 USA

[4] Podiatr Med & Surg, Pittsfield, MA 01201 USA

[5] Univ Colorado, Sch Med, Aurora, CO 80045 USA

[6] Yale Univ, New Haven, CT 06520 USA

[7] Pachyonychia Congenita Project, Salt Lake City, UT 84109 USA

来源：

JOURNAL OF DERMATOLOGICAL SCIENCE | 2015年 / 77卷 / 03期

关键词：

Painful palmoplantar keratoderma; Genodermatosis; Monogenic skin disorder; mTOR signaling pathway; Keratinocyte; Desquamation; EPIDERMOLYTIC PALMOPLANTAR KERATODERMA; KERATIN; 9; ECTODERMAL DYSPLASIA; LAMELLAR GRANULES; MOLECULAR-CLONING; PROTEIN-SYNTHESIS; NAIL DEFECTS; MUTATION; DISEASE; PSORIASIS;

D O I：

10.1016/j.jdermsci.2015.01.001

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

引用

页码：156 / 165

页数：10

共 80 条

[21] Evidence for local control of gene expression in the epidermal differentiation complex [J].