The effects of mechanical stress on cellular senescence in adult progeria Werner syndrome

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23939
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Chiba University
• Principal Investigator: Kato Hisaya 千葉大学, 医学部附属病院, 助教 (90841974)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 早老症 / 老化 / ウェルナー症候群 / 線維芽細胞

Outline of Final Research Achievements

Adult progeria Werner syndrome exhibits symptoms similar to general human aging (cataracts, diabetes, malignant tumors, etc.) at a young age. On the other hand, there are WS-specific symptoms such as refractory skin ulcers and sarcomas, which are mainly involved in organs with mesenchymal origin. The cause of this disease phenotype is unclear. This study focused on intractable skin ulcers, which are one of the major factors that distress patients, and their relationship with mechanical stress. As a result, the foot fibroblasts derived from WS patients showed a phenotype different from that of the trunk fibroblasts. These findings may be useful for future pathological elucidation and therapeutic development.

Free Research Field

老化

Academic Significance and Societal Importance of the Research Achievements

WS患者の四肢は、皮下脂肪が萎縮し、石灰化を伴う難治性皮膚潰瘍を高頻度に伴う一方、体幹の皮膚には明らかな異常は見られない。しかしその差が生じる機序は不明であった。今回我々は2名のWS患者の足部および体幹から皮膚線維芽細胞を樹立し、表現型を比較した。その結果、足部由来線維芽細胞は体幹由来に比し、脂肪・軟骨分化能が低下している一方、骨分化能は同等に保たれていた。これらの結果はWSの難治性皮膚潰瘍と密接に関連している可能性があり、今後の治療開発への応用が期待される。