Abstract
Background
Lichen planopilaris (LPP) and pseudopelade of Brocq (PPB) are two scarring alopecia
diagnoses that exhibit similar clinical features. Some suggest LPP and PPB are not
distinct diseases, but rather different clinical presentations in a spectrum derived
from the same underlying pathogenic mechanism.
Objective
We explored the degree of similarity between LPP and PPB gene expression patterns
and the potential for common and unique gene pathway and gene activity in LPP and
PPB using microarrays.
Methods
Microarray analysis, using a 21K cDNA set, was performed on pairs of biopsies obtained
from affected and unaffected scalp of untreated patients. Diagnosis was confirmed
by histopathology. Significantly differentially expressed genes were identified by
analysis of microarray results in various datasets and screened for signaling pathway
involvement. Selected genes were validated by quantitative PCR and immunohistology.
Results
The global gene expression profiles in LPP and PPB versus comparative intra-control
scalp tissue were distinguishable by significance analysis of microarrays (SAM). There
was limited commonality in the gene expression profiles between LPP and PPB. Specific
genes, such as MMP11, TNFSF13B, and APOL2, were identified with significantly differential expression in association with LPP
versus PPB.
Conclusions
Our findings may have important implications for understanding the pathogenesis of
LPP and PPB at the molecular level. Results suggest LPP and PPB involve different
mechanisms of disease development and should be regarded as biologically distinct
cicatricial alopecia diagnoses. Genes that we have identified may be useful as markers
of the respective diagnoses and may be potential therapeutic targets.
Abbreviations:
APOL2 (apolipoprotein L2), FDR (false discovery rate), GO (Gene Ontology), LPP (lichen planopilaris), MMP11 (matrix metallopeptidase 11), PPB (pseudopelade of Brocq), qPCR (quantitative reverse transcriptase PCR), TNFSF13B (tumor necrosis factor (ligand) superfamily, member 13b)Keywords
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References
- Cicatricial alopecia: clinico-pathological findings and treatment.Clin Dermatol. 2001; 19: 211-225
- Diagnosis and management of primary cicatricial alopecia: part II.SKINmed. 2008; 7: 78-83
- Diagnosis and management of primary cicatricial alopecia: part I.SKINmed. 2008; 7: 19-26
- Distribution of Langerhans cells in human hair follicle.J Cutan Pathol. 1997; 24: 636-640
- Etiology of cicatricial alopecias: a basic science point of view.Dermatol Ther. 2008; 21: 212-220
- Update on primary cicatricial alopecias.J Am Acad Dermatol. 2005; 53 (quiz 38–40): 1-37
- Pseudopelade.Arch Dermatol. 1960; 82: 336-343
- The cicatricial alopecias: an historical and clinical-review and an histologic investigation.J Invest Dermatol. 1947; 8: 99-122
- Pseudopelade of Brocq.Dermatologica. 1986; 172: 18-23
- Massive lymphocyte-mediated apoptosis during the early stage of pseudopelade.Dermatologica. 1986; 172: 254-257
- What is pseudopelade?.Clin Exp Dermatol. 1992; 17: 305-306
- Pseudopelade de Brocq.Maloire Publishers, Paris1930
- A clinicopathological study of scarring alopecia.Br J Dermatol. 1993; 128: 533-536
- Cicatricial alopecia; a dermatopathologic and immunopathologic study of 33 patients (pseudopelade of Brocq is not a specific clinico-pathologic entity).Int J Dermatol. 2002; 41: 8-15
- A multiparametric approach is essential to define different clinicopathological entities within pseudopelade of Brocq: reply from authors.Br J Dermatol. 2002; 146: 532-533
- Pseudopeladic state; comments on one hundred cases of circumscribed cicatricial alopecia, apparently primary, of pseudopelade type.Ann Dermatol Syphiligr (Paris). 1954; 81: 5-26
- Advances in spotted microarray resources for expression profiling.Brief Funct Genomic Proteomic. 2003; 2: 21-30
- Application of gene microarrays in the study of prostate cancer.Methods Mol Med. 2003; 81: 299-320
- Significance analysis of microarrays applied to the ionizing radiation response.Proc Natl Acad Sci USA. 2001; 98: 5116-5121
- The Gene Ontology (GO) database and informatics resource.Nucleic Acids Res. 2004; 32: D258-261
- The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists.Genome Biol. 2007; 8: R183
- A network-based analysis of systemic inflammation in humans.Nature. 2005; 437: 1032-1037
- Matrix metalloproteinases-2,-3,-7 -9 and -10, but not MMP-11, are differentially expressed in normal, benign tumorigenic and malignant human keratinocyte cell lines.Biol Chem. 2000; 381: 497-507
- Matrix metalloproteinases in asthma and COPD.Curr Opin Pharmacol. 2005; 5: 257-263
- Expression of stromelysin-3 (matrix metalloproteinase-11) in macrophages of murine thymus following thymocyte apoptosis.Cell Immunol. 2005; 235: 21-28
- Metalloproteinases and their inhibitors in matrix remodeling.Trends Genet. 1990; 6: 121-125
- Membrane proteases: roles in tissue remodeling and tumour invasion.Curr Opin Cell Biol. 1992; 4: 802-809
- Structure and promoter characterization of the human stromelysin-3 gene.J Biol Chem. 1995; 270: 20337-20344
- The expression of matrix metalloproteinase-11 protein in various types of glomerulonephritis.Nephrol Dial Transplant. 2007; 22: 109-117
- Stromelysin 3 expression: a useful marker for the differential diagnosis dermatofibroma versus dermatofibrosarcoma protuberans.J Am Acad Dermatol. 2002; 46: 408-413
- Breast-cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing.J Invest Dermatol. 1992; 99: 870-872
- Stromelysin-3 expression by mammary tumor-associated fibroblasts under in vitro breast cancer cell induction.Int J Cancer. 2002; 99: 792-799
- Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway.BMC Cancer. 2007; 7: 12
- Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans.Br J Cancer. 1996; 73: 1401-1408
- Hereditary absence of sebaceous glands in the mouse.Science. 1965; 148: 1471-1473
- Hereditary defect of the pilosebaceous unit in a new double mutant mouse.J Invest Dermatol. 1969; 52: 115-118
- Transection level dictates the pattern of hair follicle sheath growth in vitro.Dev Biol. 1994; 165: 469-479
- Insights from the asebia mouse: a molecular sebaceous gland defect leading to cicatricial alopecia.J Cutan Pathol. 2001; 28: 445-447
- Defolliculated (dfl): a dominant mouse mutation leading to poor sebaceous gland differentiation and total elimination of pelage follicles.J Invest Dermatol. 2002; 119: 32-37
- Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia.J Invest Dermatol. 2009; 129: 1243-1257
- The human apolipoprotein L gene cluster: identification, classification, and sites of distribution.Genomics. 2001; 74: 71-78
- The function of apolipoproteins L.Cell Mol Life Sci. 2006; 63: 1937-1944
- Association of SNPs and haplotypes in APOL1, 2 and 4 with schizophrenia.Schizophr Res. 2008; 104: 153-164
- Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22.Proc Natl Acad Sci USA. 2002; 99: 4680-4685
- Cracking the BAFF code.Nat Rev Immunol. 2009; 9: 491-502
- Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas.Pharmacol Ther. 2006; 112: 774-786
- The role of the BAFF/APRIL system on T cell function.Semin Immunol. 2006; 18: 284-289
- BAFF-targeting therapy, a promising strategy for treating autoimmune diseases.Eur J Pharmacol. 2008; 597: 1-5
- BAFF blockade for systemic lupus erythematosus: will the promise be fulfilled?.Immunol Rev. 2008; 223: 156-174
Article info
Publication history
Published online: July 12, 2010
Accepted:
October 22,
2009
Received in revised form:
October 19,
2009
Received:
April 2,
2009
Identification
Copyright
© 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.