TRIOBP điều chỉnh tín hiệu β-catenin thông qua sự điều hòa của miR-29b trong bệnh xơ phổi vô căn

Lan Wang1,2,3,4, Wenchao Zhao1,2,3,4, Cong Xia1,2,4,3, SF Ma1,3,4,2, Zhongzheng Li1,2,3,4, Ningdan Wang1,2,3,4, Linke Ding1,2,3,4, Yaxuan Wang1,2,3,4, Cheng Liu1,2,3,4, Huibing Liu2,3,4,1, Juntang Yang1,2,3,4, Yajun Li1,2,3,4, Iván O. Rosas5, Guoying Yu1,2,3,4
1Henan International Joint Laboratory of Pulmonary Fibrosis
2College of Life Science, Henan Normal University, 46 Jianshe Road, Xinxiang, 453007, Henan, China
3State Key Laboratory of Cell Differentiation and Regulation
4Henan Center for Outstanding Overseas Scientists of Organ Fibrosis
5Division of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

Tóm tắt

Tóm tắtBệnh xơ phổi vô căn (IPF) là một căn bệnh phổi gây tử vong và tàn phá, có nguyên nhân chưa được xác định, được mô tả như là kết quả của nhiều chu kỳ tổn thương tế bào biểu mô và kích hoạt nguyên bào sợi. Dù sự hiểu biết về căn bệnh này đã tăng lên đáng kể, nhưng vẫn chưa có liệu pháp nào có khả năng đảo ngược hình thức xơ hóa này. Trong nghiên cứu trước đây của chúng tôi, chúng tôi đã phát hiện rằng miR-29b có tác dụng trị liệu trên xơ phổi. Tuy nhiên, cơ chế chống xơ hóa của nó vẫn chưa rõ ràng. Gần đây, nghiên cứu của chúng tôi đã xác định rằng Protein liên kết F-Actin (TRIOBP) là một trong những gen mục tiêu của miR-29b và phát hiện rằng sự thiếu hụt của TRIOBP làm tăng khả năng kháng xơ phổi ở in vivo. Việc giảm TRIOBP đã ức chế sự phân chia của tế bào biểu mô và giảm thiểu sự kích hoạt của nguyên bào sợi. Ngoài ra, sự thiếu hụt của yếu tố trao đổi nucleotide guanine Trio (TRIO) trong tế bào biểu mô và nguyên bào sợi làm giảm tính nhạy cảm với xơ phổi. TRIOBP tương tác với TRIO đã thúc đẩy sự giao thoa bất thường giữa biểu mô - trung mô và điều chỉnh sự dịch chuyển nhân chất tế bào của β-catenin. Chúng tôi kết luận rằng trục miR-29b–TRIOBP–TRIO–β-catenin có thể là một trục chống xơ hóa quan trọng trong IPF, giúp điều chỉnh sự tái sinh và xơ hóa phổi, điều này có thể cung cấp một chiến lược điều trị hứa hẹn cho xơ phổi. Tóm tắt hình ảnh

Từ khóa


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