Investigation of association between adipocytes and vasculopathy of systemic sclerosis by Fli1 knockout model

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24041
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Miyagawa Takuya 東京大学, 医学部附属病院, 助教 (60843323)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 全身性強皮症 / 血管障害 / 脂肪細胞

Outline of Final Research Achievements

Association between adipocytes and vasculopathy of systemic sclerosis (SSc) remains to be seen. We generated adipocyte-specific Fli1 knockout (Fli1 AdipoKO) mice and investigated whether and how vasculopathy is induced. Fli1 AdipoKO mice exhibited vascular structural and functional abnormalities as early as 3 months of age. Bone marrow-derived mesenchymal stem cells (BM-MSCs) of Fli1 AdipoKO mice exhibited de-differentiated phenotype, suggesting the contribution of defective vasculogenesis to the development of vascular abnormalities. This phenotype was induced by co-culture of Fli1-deficient adipocytes and BM-MSCs of wild type mice. Furthermore, upregulated IL-6 induced by Fli1-deficient adipocytes changed BM-MSCs of wild type mice into de-differentiated phenotype. These results indicate that Fli1-deficient adipocytes can be involved in the development of vasculopathy recapitulating SSc, suggesting a contribution of phenotypically altered adipocytes to the development of SSc.

Free Research Field

全身性強皮症、皮膚悪性腫瘍などの皮膚科難病領域

Academic Significance and Societal Importance of the Research Achievements

今まで明らかになっていなかった全身性強皮症の血管障害と脂肪細胞の関連が本研究によって示唆された。また全身性強皮症の血管障害の病態にもIL-6が関与している可能性があり、抗IL-6抗体による治療が線維化のみならず血管障害の改善にも寄与する可能性があることが示唆された。