| Project/Area Number |
16K10163
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kochi University |
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Principal Investigator |
TERAISHI MIKA 高知大学, 教育研究部医療学系臨床医学部門, 助教 (40437736)
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| Co-Investigator(Kenkyū-buntansha) |
高石 樹朗 高知大学, 教育研究部医療学系臨床医学部門, 助教 (10303223)
中島 喜美子 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (20403892)
佐野 栄紀 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Mowat-Wilson症候群 / ZEB2 / コラーゲン合成 |
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| Outline of Final Research Achievements |
Mowat-Wilson syndrome (MOWS) is a congenital disease caused by ZEB2 mutation. MOWS patients show intellectual disability, distinctive facial appearance, microcephaly, and so on. However, the skin manifestation has not been documented in detail. Here, we recognized that MOWS patients exhibit Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated skin manifestations similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, whereas molecules involved in degradation of the ECM were up-regulated. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまで皮膚症状について検討されていなかったMOWS患者に、EDS患者様の症状が出現することを初めて見出した。このことは、MOWSの病態にEDSと同様のコラーゲン線維形成の異常を示す疾患という概念を与えただけでなく、コラーゲン合成におけるZEB2の関与を示す一因となった。今後、コラーゲン合成におけるZEB2の役割について詳細に検討することで、皮膚だけでなく全身の臓器に生じる線維化疾患に、ZEB2という新たな方向からの治療戦略を与えた。
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