Brn2 is a transcription factor regulating keratinocyte differentiation with a possible role in the pathogenesis of lichen planus.
Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions.
Shi
Ge
G
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Sohn
Kyung-Cheol
KC
Choi
Dae-Kyoung
DK
Kim
Yu-Jin
YJ
Kim
Seong-Jin
SJ
Ou
Bai-Sheng
BS
Piao
Yong-Jun
YJ
Lee
Young Ho
YH
Yoon
Tae-Jin
TJ
Lee
Young
Y
Seo
Young-Joon
YJ
Kim
Chang Deok
CD
Lee
Jeung-Hoon
JH
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D000091344:Filaggrin Proteins; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D050809:POU Domain Factors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors; C085076:transcription factor Brn-2