Epithelial-fibroblast interactions in IPF: Lessons from in vitro co-culture studies

IF 2.2 3区生物学 Q4 CELL BIOLOGY Differentiation Pub Date : 2023-09-12 DOI:10.1016/j.diff.2023.09.001

J. Brussow , K. Feng , F. Thiam , S. Phogat , E.T. Osei

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引用次数: 1

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease that is characterized by increased cellular proliferation and differentiation together with excessive extracellular matrix (ECM) deposition leading to buildup of scar tissue (fibrosis) and remodeling in the lungs. The activated and differentiated (myo)fibroblasts are one of the main sources of tissue remodeling in IPF and a crucial mechanism known to contribute to this feature is an aberrant crosstalk between pulmonary fibroblasts and the abnormal or injured pulmonary epithelium. This epithelial-fibroblast interaction mimics the temporal, spatial and cell-type specific crosstalk between the endoderm and mesoderm in the so-called epithelial-mesenchymal trophic unit (EMTU) during lung development that is proposed to be activated in healthy lung repair and dysregulated in various lung diseases including IPF. To study the dysregulated lung EMTU in IPF, various complex in vitro models have been established. Hence, in this review, we will provide a summary of studies that have used complex (3-dimensional) in vitro co-culture, and organoid models to assess how abnormal epithelial-fibroblast interactions in lung EMTU contribute to crucial features of the IPF including defective cellular differentiation, proliferation and migration as well as increased ECM deposition.

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IPF中上皮成纤维细胞的相互作用：体外共培养研究的经验教训。

特发性肺纤维化（IPF）是一种进行性间质性疾病，其特征是细胞增殖和分化增加，细胞外基质（ECM）沉积过多，导致肺部瘢痕组织（纤维化）和重塑。活化和分化的（myo）成纤维细胞是IPF组织重塑的主要来源之一，已知导致这一特征的关键机制是肺成纤维细胞与异常或损伤的肺上皮之间的异常串扰。这种上皮-成纤维细胞的相互作用模拟了肺发育过程中所谓的上皮-间充质营养单位（EMTU）中内胚层和中胚层之间的时间、空间和细胞类型特异性串扰，该单位被认为在健康的肺修复中被激活，在包括IPF在内的各种肺部疾病中被失调。为了研究IPF中失调的肺EMTU，已经建立了各种复杂的体外模型。因此，在这篇综述中，我们将总结使用复杂（三维）体外共培养和类器官模型来评估肺EMTU中异常的上皮-成纤维细胞相互作用如何导致IPF的关键特征，包括细胞分化、增殖和迁移缺陷以及ECM沉积增加的研究。

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

Differentiation 生物-发育生物学

CiteScore

4.10

自引率

3.40%

发文量

审稿时长

51 days

期刊介绍： Differentiation is a multidisciplinary journal dealing with topics relating to cell differentiation, development, cellular structure and function, and cancer. Differentiation of eukaryotes at the molecular level and the use of transgenic and targeted mutagenesis approaches to problems of differentiation are of particular interest to the journal. The journal will publish full-length articles containing original work in any of these areas. We will also publish reviews and commentaries on topics of current interest. The principal subject areas the journal covers are: • embryonic patterning and organogenesis • human development and congenital malformation • mechanisms of cell lineage commitment • tissue homeostasis and oncogenic transformation • establishment of cellular polarity • stem cell differentiation • cell reprogramming mechanisms • stability of the differentiated state • cell and tissue interactions in vivo and in vitro • signal transduction pathways in development and differentiation • carcinogenesis and cancer • mechanisms involved in cell growth and division especially relating to cancer • differentiation in regeneration and ageing • therapeutic applications of differentiation processes.

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