Identification of transcriptional targets of Wnt/beta-catenin signaling in dermal papilla cells of human scalp hair follicles: EP2 is a novel transcriptional target of Wnt3a

J Dermatol Sci. 2010 May;58(2):91-6. Epub 2010 Mar 6.

Identification of transcriptional targets of Wnt/beta-catenin signaling in dermal papilla cells of human scalp hair follicles: EP2 is a novel transcriptional target of Wnt3a.
Shin H, Kwack MH, Shin SH, Oh JW, Kang BM, Kim AA, Kim J, Kim MK, Kim JC, Sung YK.

Department of Immunology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.

Abstract
BACKGROUND: Recent studies showed that Wnt signaling through the beta-catenin pathway (canonical Wnt signaling) act on mouse dermal papilla cells (DPCs) enabling hair follicles to keep growing. OBJECTIVE: To investigate whether human DPCs respond to canonical Wnt signaling and, if so, to identify target genes of Wnt/beta-catenin pathway. METHODS: Cultured human DPCs were transiently transfected with the beta-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of beta-catenin signaling by Wnt3a (one of the canonical Wnts). Immunofluorescence staining was also performed to localize beta-catenin in the presence or absence of Wnt3a. Microarray was carried out using Affymetrix gene chips. RT-PCR analysis and immunoblot were employed to verify microarray data. Cyclic AMP (cAMP) levels were measured using EIA assay after Wnt3a and PGE2 treatment in DPCs. RESULTS: Wnt3a significantly stimulated the transcriptional activity of pTopflash but not pFopflash. In line with this, we identified a number of genes that are regulated by Wnt3a. Some of the differently expressed genes including EP2 were confirmed by RT-PCR analysis. Immunoblot further confirmed that EP2 protein is indeed increased by Wnt3a. DPCs pretreated with Wnt3a showed higher responsiveness to PGE2 as measured by cAMP levels. CONCLUSIONS: Elucidation of the role of Wnt3a-regulated genes identified in this study including EP2 would help our understanding of hair-induction and maintenance of anagen phase. 2010 Japanese Society for Investigative Dermatology.

I'm wondering why all these breakthroughs and actual advancements are all being contributed mostly by Japanese researchers. They mostly all have awesome hair.

Dave228 - A lot of good research comes out of Japan & many non-US places where the medicine is integrative. Less emphasis on making profits and more on efficacy.