Activation of the OVOL1-OVOL2 axis in the hair bulb and in pilomatricoma

Takamichi Ito, Gaku Tsuji, Fumitaka Ohno, Hiroshi Uchi, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Yuichi Yoshida, Osamu Yamamoto, Yoshinao Oda, Masutaka Furue

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

OVOL1 and OVOL2, ubiquitously conserved genes encoding C2H2 zinc finger transcription factors in mammals, control epithelial cell proliferation, and differentiation, including those in skin. OVOL1 and OVOL2 expression is coordinately mediated via the Wnt signaling pathway, and OVOL1 negatively regulates OVOL2 expression in a transcriptional manner. Our previous study of OVOL1 expression in human skin revealed that OVOL1 is preferentially expressed in the inner root sheath of the hair follicle. Therefore, we hypothesized that the OVOL1-OVOL2 axis is involved in normal and neoplastic follicular differentiation. Immunohistochemical analysis showed that OVOL1 and OVOL2 were strongly expressed in a mutually exclusive manner in the cytoplasm of inner root sheath cells and matrix cells, respectively, in normal follicles. OVOL2 was also expressed in pilomatricoma, with only partial expression of OVOL1. Cultured human keratinocytes expressed OVOL1 and OVOL2 on both the mRNA and protein levels. The expression of OVOL2 was higher in keratinocytes transfected with siRNA of OVOL1. Ketoconazole, a hair growth stimulant, up-regulated the expression of OVOL1 but did not affect OVOL2 expression. These results indicated that the OVOL1-OVOL2 axis may actively contribute to cell differentiation and proliferation in the hair bulb, suggesting that the OVOL1 and OVOL2 may be therapeutic targets of hair disorders, including alopecia, and play important roles in the tumorigenesis of pilomatricoma.

Original languageEnglish
Pages (from-to)1036-1043
Number of pages8
JournalAmerican Journal of Pathology
Volume186
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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Pilomatrixoma
Hair
Keratinocytes
Cell Differentiation
Cell Proliferation
Skin
Wnt Signaling Pathway
Ketoconazole
Hair Follicle
Alopecia
Small Interfering RNA
Mammals
Carcinogenesis
Cytoplasm
Transcription Factors
Epithelial Cells
Messenger RNA
Growth
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Activation of the OVOL1-OVOL2 axis in the hair bulb and in pilomatricoma. / Ito, Takamichi; Tsuji, Gaku; Ohno, Fumitaka; Uchi, Hiroshi; Nakahara, Takeshi; Hashimoto-Hachiya, Akiko; Yoshida, Yuichi; Yamamoto, Osamu; Oda, Yoshinao; Furue, Masutaka.

In: American Journal of Pathology, Vol. 186, No. 4, 01.04.2016, p. 1036-1043.

Research output: Contribution to journalArticle

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