Development of novel estrogen treatment for vocal fold scar

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18813
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Mukudai Shigeyuki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00821860)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 声帯瘢痕 / エストロゲン / TGF-β/Smad signaling

Outline of Final Research Achievements

Vocal fold fibrosis remains a significant clinical challenge. Estrogens, steroid hormones predominantly responsible for secondary sexual characteristics in women, have been shown to alter wound healing. We sought to elucidate the effects of estrogens on TGF-β1 signaling in vocal fold fibroblasts (VFFs). VFFs were isolated from 10-week-old, male SD rats, and ERα and GPR30 were examined via immunostaining and qPCR. VFFs were treated with estradiol (E2, 10-7, 10-8 or 10-9 M) ± TGF-β1 (10 ng/mL). qPCR was employed to determine estrogen receptor-mediated effects of E2 on genes related to fibrosis. ERα and GPR30 were expressed in VFFs. The combination of E2 (10－8 M) and TGF-β1 significantly increased Smad7 and decreased Col1a1 compared to TGF- β1 alone. E2 regulated TGF-β1/Smad signaling via estrogen receptors in VFFs. These findings provide insight into potential mechanisms of estrogens on vocal fold injury with the goal of enhanced therapeutics for vocal fold fibrosis.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

声帯瘢痕は難治性線維化疾患であり、音声障害による生活上のダメージは大きい。従来からグルココルチコイドの局所注入が行われてきたが、その効果は不確実である。近年、性ステロイドに属するエストロゲンが創傷治癒に対して保護作用を有することが報告されているが、声帯創傷治癒に対する効果は不明であった。本研究ではエストロゲンが声帯の創傷治癒過程に与える影響を、声帯線維芽細胞を用いて分子生物学的に解明した。本研究の成果はエストロゲンを用いた声帯瘢痕治療への臨床応用につながり、声帯瘢痕がもたらす音声障害を克服する切り札を提供すると考えられる。