ZC3H4 governs epithelial cell migration through ROCK/p-PYK2/p-MLC2 pathway in silica-induced pulmonary fibrosis

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2023-11-01 DOI:10.1016/j.etap.2023.104301

Rong Jiang , Yichao Zhou , Qianqian Gao , Lei Han , Zhen Hong

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引用次数: 0

Abstract

Background

Increased epithelial migration capacity is a key step accompanying epithelial-mesenchymal transition (EMT). Our lab has described that ZC3H4 mediated EMT in silicosis. Here, we aimed to explore the mechanisms of ZC3H4 by which to stimulate epithelial cell migration.

Methods

Silicon dioxide (SiO₂)-induced pulmonary fibrosis (PF) animal models were administered by intratracheal instillation in C57BL/6 J mice. Pathological analysis and 2D migration assay were established to uncover the pulmonary fibrotic lesions and epithelial cell migration, respectively. Inhibitors targeting ROCK/p-PYK2/p-MLC2 and CRISPR/Cas9 plasmids targeting ZC3H4 were administrated to explore the signaling pathways.

Results

1) SiO₂ upregulated epithelial migration in pulmonary fibrotic lesions. 2) ZC3H4 modulated SiO₂-induced epithelial migration. 3) ZC3H4 governed epithelial migration through ROCK/p-PYK2/p-MLC2 signaling pathway.

Conclusions

ZC3H4 regulates epithelial migration through the ROCK/p-PYK2/p-MLC2 signaling pathway, providing the possibility that molecular drugs targeting ZC3H4-overexpression may exert effects on pulmonary fibrosis induced by silica.

查看原文本刊更多论文

ZC3H4在二氧化硅诱导的肺纤维化中通过ROCK/p-PYK2/p-MLC2途径调控上皮细胞迁移。

背景：增加上皮迁移能力是伴随上皮-间充质转化（EMT）的关键步骤。我们的实验室已经描述了ZC3H4介导的矽肺EMT。在此，我们旨在探索ZC3H4刺激上皮细胞迁移的机制。方法：采用C57BL/6J小鼠气管内滴注二氧化硅（SiO2）诱导的肺纤维化（PF）动物模型。建立病理学分析和2D迁移试验，分别揭示肺纤维化病变和上皮细胞迁移。给药靶向ROCK/p-PYK2/p-MLC2的抑制剂和靶向ZC3H4的CRISPR/Cas9质粒以探索信号通路。结果：1）SiO2可上调肺纤维化病变上皮细胞迁移。2） ZC3H4调节SiO2诱导的上皮迁移。3） ZC3H4通过ROCK/p-PYK2/p-MLC2信号通路调控上皮迁移。结论：ZC3H4通过ROCK/p-PYK2/p-MLC2信号通路调节上皮迁移，为靶向ZC3H4过表达的分子药物对二氧化硅诱导的肺纤维化发挥作用提供了可能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.