Versican gene: Regulation by the β-catenin signaling pathway plays a significant role in dermal papilla cell aggregative growth

Background: Dermal papilla cells (DPCs), which exhibit a multilayer aggregative growth character in in vitro culture, are closely related to induction of hair follicles (HFs) formation, and are associated with the development and cycle regulation of HFs. Versican, a large chondroitin sulfate proteoglycan and one of the major components of the extracellular matrix, plays an essential role in hair follicle formation. And also the Wnt/beta-catenin signaling pathway performs a crutial function in induction during hair follicle growth and embryogenesis. Objective: To characterize the role of versican and beta-catenin in regulating DPCs aggregative growth, and to explore the versican gene expression regulation mechanism by TCF-4/beta-catenin signaling pathway. Methods: We first cultured DPCs at different passages, and detected the change in beta-catenin and versican expression in DPCs of various passages by RT-PCR and Western blot. Then we knockdowned the versican and beta-catenin gene, evaluated and verificated the binding capability of TCF-4/beta-catenin to TOP elements in versican gene promoter region at varied passage DPCs by EMSA and ChIP Assay, finally observed the effect of Wnt/beta-catenin pathway inhibition on DPC aggregative growth. Results: With the increase of passage, DPCs lost the aggregative property, the versican mRNA and protein level in DPCs was on a gradual decline, while not significant declining tendency of beta-catenin. The mRNA of both beta-catenin and versican reduced simultaneously after beta-catenin siRNA transfection. The binding ability of TCF-4/beta-catenin of varied-passage DPCs to cultured versican promoters diminished with the increase of DPC passages. And versican inhibition or Wnt/beta-catenin pathway blocking could both produce considerable effect on the aggregative growth of low-passage DPCs. Conclusion: Wnt/beta-catenin signal transducting system regulates DPC aggregative growth through modifying versican expression by means of acting on the versican gene upstream promoter. (C) 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.