Hedgehog signaling in murine and human

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Chiba University
• Principal Investigator: FUJII Katsunori 千葉大学, 医学(系)研究科(研究院), 講師 (70344992)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ヘッジホッグ / 形態形成 / 癌形成 / 高発癌性遺伝 / Gorlin症候群 / ゴーリン症候群 / PTCH1

Outline of Final Research Achievements

Hedgehog signaling is a pivotal developmental pathway that comprises hedgehog, PTCH1, SMO, and GLI proteins. Mutations in PTCH1 are responsible for Gorlin syndrome, which is characterized by developmental defects and tumorigenicity. In order to elucidate the mechanism by which transduction of the hedgehog signal is regulated in tissues, we employed murine C3H10T1/2 cells and human fibroblasts. We investigated GLI1 transcription to assess native signal transduction, and then treated cells with a recombinant human hedgehog protein with or without serum deprivation. Hedgehog stimulation and nutritional deprivation synergistically enhanced GLI1 transcription levels, which was blocked more efficiently by vismodegib. These results indicated that the hedgehog stimulation and nutritional deprivation synergistically activated the hedgehog signaling pathway. These fibroblasts may become a significant tool for predicting the efficacies of hedgehog molecular-targeted therapies such as vismodegib.

Free Research Field

小児神経学