Sustained amphiregulin expression in intermediate alveolar stem cells drives progressive fibrosis

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic disease. Recent studies have highlighted the persistence of an intermediate state of alveolar stem cells in IPF lungs. In this study, we discovered a close correlation between the distribution pattern of intermediate alveolar stem cells and the progression of fibrotic changes. We showed that amphiregulin (AREG) expression is significantly elevated in intermediate alveolar stem cells of mouse fibrotic lungs and IPF patients. High levels of serum AREG correlate significantly with profound deteriorations in lung function in IPF patients. We demonstrated that AREG in alveolar stem cells is both required and sufficient for activating EGFR in fibroblasts, thereby driving lung fibrosis. Moreover, pharmacological inhibition of AREG using a neutralizing antibody effectively blocked the initiation and progression of lung fibrosis in mice. Our study underscores the therapeutic potential of anti-AREG antibodies in attenuating IPF progression, offering a promising strategy for treating fibrotic diseases.

Abstract Image

中间肺泡干细胞中持续表达两性胰岛素会导致渐进性纤维化
特发性肺纤维化(IPF)是一种进行性的致命纤维化疾病。最近的研究强调,在IPF肺中,肺泡干细胞持续处于中间状态。在这项研究中,我们发现中间状态肺泡干细胞的分布模式与纤维化变化的进展密切相关。我们发现,在小鼠纤维化肺和IPF患者的中间肺泡干细胞中,安非拉酮(AREG)的表达明显升高。高水平的血清 AREG 与 IPF 患者肺功能的严重恶化密切相关。我们证实,肺泡干细胞中的 AREG 是激活成纤维细胞中表皮生长因子受体的必要条件和充分条件,从而推动肺纤维化。此外,使用中和抗体对 AREG 进行药理抑制,可有效阻止小鼠肺纤维化的发生和发展。我们的研究强调了抗AREG抗体在减轻IPF进展方面的治疗潜力,为治疗纤维化疾病提供了一种前景广阔的策略。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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