Epithelial IL5RA promotes epithelial-mesenchymal transition in pulmonary fibrosis via Jak2/STAT3 cascade

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Shuyun Chen, Tiantian Zhao, Shiguang Xie, Xuan Wan
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引用次数: 0

Abstract

Pulmonary fibrosis is a progressive and debilitating lung disease characterized by the excessive accumulation of extracellular matrix (ECM) components within the lung parenchyma. However, the underlying mechanism remains largely elusive, and the treatment options available for pulmonary fibrosis are limited. Interleukin 5 receptor, alpha (IL5RA) is a well-established regulator of eosinophil activation, involved in eosinophil-mediated anti-parasitic activities and allergic reactions. Recent studies have indicated additional roles of IL5RA in lung epithelium and fibroblasts. Nevertheless, its involvement in pulmonary fibrosis remains unclear. In present study, we employed single-cell analyses alongside molecular and cellular assays to unveil the expression of IL5RA in lung epithelial cells. Moreover, using both in vitro and in vivo models, we demonstrated a notable upregulation of epithelial IL5RA during the progression of pulmonary fibrosis. This upregulated IL5RA expression subsequently promotes epithelial-mesenchymal transition (EMT), leading to the generation of mesenchymal phenotype with augmented capability for ECM production. Importantly, our findings uncovered that the pro-fibrotic function of IL5RA is mediated by Jak2/STAT3 signaling cascades. Inhibiting IL5RA has the potential to deactivate Jak2/STAT3 and suppress the downstream EMT process and ECM production, thereby offering a promising therapeutic strategy for pulmonary fibrosis.

上皮细胞 IL5RA 通过 Jak2/STAT3 级联促进肺纤维化中的上皮-间质转化
肺纤维化是一种进行性肺部疾病,使人衰弱,其特点是细胞外基质(ECM)成分在肺实质内过度积聚。然而,肺纤维化的基本机制仍然难以捉摸,可用于治疗肺纤维化的方法也很有限。白细胞介素 5 受体α(IL5RA)是一种公认的嗜酸性粒细胞活化调节因子,参与嗜酸性粒细胞介导的抗寄生虫活动和过敏反应。最近的研究表明,IL5RA 在肺上皮细胞和成纤维细胞中还有其他作用。然而,它在肺纤维化中的参与仍不清楚。在本研究中,我们采用了单细胞分析以及分子和细胞检测方法来揭示 IL5RA 在肺上皮细胞中的表达。此外,通过体外和体内模型,我们证实了在肺纤维化进展过程中上皮细胞 IL5RA 的显著上调。上调的 IL5RA 表达随后会促进上皮-间充质转化(EMT),导致间充质表型的产生,并增强 ECM 的生成能力。重要的是,我们的研究结果发现,IL5RA 的促纤维化功能是由 Jak2/STAT3 信号级联介导的。抑制 IL5RA 有可能使 Jak2/STAT3 失活,并抑制下游的 EMT 过程和 ECM 生成,从而为肺纤维化提供一种有前景的治疗策略。
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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
41
审稿时长
42 days
期刊介绍: Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.
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