si-Tgfbr1-loading liposomes inhibit shoulder capsule fibrosis via mimicking the protective function of exosomes from patients with adhesive capsulitis

Yaying Sun; Yisheng Chen; Jinrong Lin; Yuhan Zhang; Beijie Qi; Jiwu Chen

doi:https://doi.org/10.1186/s40824-022-00286-2

추천

검색

자료유형: 학술저널

저자정보: Yaying Sun (Fudan University Shanghai China) Yisheng Chen (Fudan University Shanghai China) Jinrong Lin (Fudan University Shanghai China) Yuhan Zhang (Fudan University Shanghai China) Beijie Qi (Fudan University Shanghai China) Jiwu Chen (Shanghai Jiaotong University Shanghai China)

저널정보: 한국생체재료학회 생체재료학회지 생체재료학회지 제26권 제3호

발행연도: 2022.9

수록면: 649 - 663 (15page)

DOI: https://doi.org/10.1186/s40824-022-00286-2

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Background: Adhesive capsulitis is a common shoulder disorder inducing joint capsule fibrosis and pain. When combined with rotator cuff tear (RCT), treatments can be more complex. Currently, targeted therapy is lacking. Since adhesive capsulitis is reported to be related to circulating materials, we analyzed the contents and biology of circu lating exosomes from RCT patients with and without adhesive capsulitis, in an attempt to developing a targeting treatment. Methods: Samples from a consecutive cohort of patients with RCT for surgery were collected. Circulating exoso mal miRNAs sequencing were used to detect differentially expressed miRNAs in patients with and without adhesive capsulitis. For experiments in vitro, Brdu staining, CCK-8 assay, wound healing test, collagen contraction test, real-time quantitative polymerase chain reaction, and western blot were conducted. Histological and immunofluorescent stain ing, and biomechanical analysis were applied in a mouse model of shoulder stiffness. The characteristics of liposomes loaded with siRNA were measured via dynamic light scattering or electron microscopy. Results: Circulating exosomal miRNAs sequencing showed that, compared to exosomes from patients without adhesive capsulitis, miR-142 was significantly up-regulated in exosomes from adhesive capsulitis (Exo-S). Both Exo-S and miR-142 could inhibit fibrogenesis, and the anti-fibrotic effect of Exo-S relied on miR-142. The target of miR-142 was proven to be transforming growth factor β receptor 1 (Tgfbr1). Then, liposomes were developed and loaded with si-Tgfbr1. The si-Tgfbr1-loading liposomes exhibited promising therapeutic effect against shoulder stiffness in mouse model with no evidence toxicity. Conclusion: This study showed that, in RCT patients with adhesive capsulitis, circulating exosomes are protective and have anti-fibrotic potential. This effect is related to the contained miR-142, which targets Tgfbr1. By mimicking this biological function, liposomes loaded with si-Tgfbr1 can mitigate shoulder stiffness pre-clinically

#Adhesive capsulitis #Rotator cuff tear #Circulating exosomes #miRNAs #Liposomes

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!