Systematic Analyses Identify the Anti-fibrotic Role of LncRNA TP53TG1 in IPF

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Jun 6

PMID 35661695

Authors

Jian Sun

Yingying Guo

Tingting Chen

Tongzhu Jin

Lu Ma

Liqiang Ai

Jiayu Guo

Zhihui Niu

Ruoxuan Yang

Qianqian Wang

Xiaojiang Yu

Huiying Gao

Yuhan Zhang

Wei Su

Xiaoying Song

Weihang Ji

Qing Zhang

Mengqin Huang

Xingxing Fan

Zhimin Du

Haihai Liang

Affiliations

Soon will be listed here.

Abstract

Long non-coding RNA (lncRNA) was reported to be a critical regulator of cellular homeostasis, but poorly understood in idiopathic pulmonary fibrosis (IPF). Here, we systematically identified a crucial lncRNA, p53-induced long non-coding RNA TP53 target 1 (TP53TG1), which was the dysregulated hub gene in IPF regulatory network and one of the top degree genes and down-regulated in IPF-drived fibroblasts. Functional experiments revealed that overexpression of TP53TG1 attenuated the increased expression of fibronectin 1 (Fn1), Collagen 1α1, Collagen 3α1, ACTA2 mRNA, Fn1, and Collagen I protein level, excessive fibroblasts proliferation, migration and differentiation induced by TGF-β1 in MRC-5 as well as PMLFs. In vivo assays identified that forced expression of TP53TG1 by adeno-associated virus 5 (AAV5) not only prevented BLM-induced experimental fibrosis but also reversed established lung fibrosis in the murine model. Mechanistically, TP53TG1 was found to bind to amount of tight junction proteins. Importantly, we found that TP53TG1 binds to the Myosin Heavy Chain 9 (MYH9) to inhibit its protein expression and thus the MYH9-mediated activation of fibroblasts. Collectively, we identified the TP53TG1 as a master suppressor of fibroblast activation and IPF, which could be a potential hub for targeting treatment of the disease.

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