Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia

Abstract

Background: Central centrifugal cicatricial alopecia (CCCA) is a primary cicatricial alopecia that most commonly affects women of African descent. Like CCCA, fibroproliferative disorders (FPDs) such as keloids, atherosclerosis, and fibroids are characterized by low-grade inflammation and irritation, resulting in end-stage fibrosis.

Objective: We sought to determine whether fibroproliferative genes were up-regulated in patients with CCCA.

Methods: A total of 5 patients with biopsy-proven CCCA were recruited for this study. Two scalp biopsy specimens were obtained from each patient; 1 from CCCA-affected vertex scalp and 1 from the unaffected occipital scalp. Microarray analysis was performed to determine the differential gene expression patterns.

Results: There was an upregulation of genes implicated in FPDs in patients with CCCA. Specifically, we noted increased expression of platelet derived growth factor gene (PDGF), collagen I gene (COL I), collagen III gene (COL III), matrix metallopeptidase 1 gene (MMP1), matrix metallopeptidase 2 gene (MMP2), matrix metallopeptidase 7 gene (MMP7), and matrix metallopeptidase 9 gene (MMP9) in affected scalp compared with in unaffected scalp. Significant overlap in the canonic pathways was noted between patients with CCCA and patients with both atherosclerosis and hepatic fibrosis (P < .001).

Limitations: Small sample size and the use of whole skin tissue for analysis.

Conclusion: We have identified the upregulation of critical genes implicated in FPDs in the gene expression profile of patients with CCCA. These findings may help identify future therapeutic targets for this otherwise difficult-to-treat condition.

Keywords: alopecia; central centrifugal cicatricial alopecia; cicatricial alopecia; fibroproliferative disorders; fibrosis; therapy.

Fig 1.

A total of 21,000 genes were analyzed via microarray analysis. Fibroproliferative genes of interest are highlighted. Up-regulated genes (>2 standard deviations [SDs]) are noted in red, unchanged genes (<2 SDs) are noted in gray, and down-regulated genes are noted in blue. CCCA, Central centrifugal cicatricial alopecia; COL1A1, collagen type I alpha 1 chain gene; COL1A2, collagen type II alpha 1 chain gene; COL3A1, collagen type III alpha 1 chain gene; COL5A1, collagen type V alpha 1 chain gene; COL5A2, collagen type V alpha 2 chain gene; Ctrl, control; FAP, fibroblast activation protein alpha gene; FC, fold change; FN1, fibronectin 1 gene; IGF1, insulin-like growth factor 1gene; MMP1, matrix metallopeptidase 1 gene; MMP2, matrix metallopeptidase 2 gene; MMP7, matrix metallopeptidase 7 gene; MMP8, matrix metallopeptidase 8 gene; MMP9, matrix metallopeptidase 9 gene; PDGFRA, platelet derived growth factor receptor alpha gene; PDGFRB, platelet derived growth factor receptor beta gene; Pt, patient; TGFB1, transforming growth factor beta 1 gene; TGFB2, transforming growth factor beta 2 gene; VEGFA, vascular endothelial growth factor A gene; VEGFB, vascular endothelial growth factor B gene.