WISP-1 induced by mechanical stress contributes to fibrosis and hypertrophy of the ligamentum flavum through Hedgehog-Gli1 signaling

Sun Chao; Ma Qinghong; Yin Jian; Zhang Han; Liu Xinhui

doi:10.1038/s12276-021-00636-5

추천

검색

자료유형: 학술저널

저자정보: Sun Chao (The Affiliated Jiangning Hospital with Nanjing Medical University) Ma Qinghong (The Affiliated Jiangning Hospital with Nanjing Medical University) Yin Jian (The Affiliated Jiangning Hospital with Nanjing Medical University) Zhang Han (The Affiliated Jiangning Hospital with Nanjing Medical University) Liu Xinhui (The Affiliated Jiangning Hospital with Nanjing Medical University)

저널정보: 대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제53권

발행연도: 2021.6

수록면: 1 - 12 (12page)

DOI: 10.1038/s12276-021-00636-5

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Ongoing chronic fibrosis and hypertrophy of the ligamentum flavum (LF) is an important cause of lumbar spinal canal stenosis (LSCS). Our previous work showed that WNT1-inducible signaling pathway protein 1 (WISP-1) is a critical driver of LF fibrosis. However, the potential mechanism has not been explored. Here, we found that Gli1 was upregulated in hypertrophic LF tissues and required for fibrogenesis in fibroblasts. Moreover, mechanical stretching increased the expression of WISP-1 in LF fibroblasts. Furthermore, WISP-1 induced fibrogenesis in vitro through the Hedgehog-Gli1 pathway. This conclusion was supported by the fact that WISP-1 activated the Hedgehog-Gli1 pathway in LF fibroblasts and that cyclopamine attenuated the effect of WISP-1-induced fibrogenesis. WISP-1 also promoted the transition of fibroblasts into myofibroblasts via the Hedgehog pathway. Importantly, a hypertrophic LF rabbit model induced by mechanical stress also showed pathological changes in fibrosis and elevated expression of WISP-1, Gli1, and α-SMA. Therapeutic administration of cyclopamine reduced collagen expression, fibroblast proliferation, and myofibroblast differentiation and ameliorated fibrosis in the mechanical stress-induced rabbit model. Collectively, our findings show mechanical stress/WISP-1/Hedgehog signaling as a new fibrotic axis contributing to LF hypertrophy and identify Hedgehog signaling as a therapeutic target for the prevention and treatment of LF fibrosis.

참고문헌 (0)

참고문헌 신청

참고문헌이 DBpia에서 서비스 중이라면, [참고문헌 신청]을 통해 등록해보세요

함께 읽어보면 좋을 논문

논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!