Pneumocystis carinii infection drives upregulation of Fn1 expression that causes pulmonary fibrosis with an inflammatory response

IF 1.5 4区生物学 Q4 MYCOLOGY

Revista Iberoamericana De Micologia Pub Date : 2024-01-01 DOI:10.1016/j.riam.2024.04.002

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引用次数: 0

Abstract

Background

Pneumocystis carinii is an opportunistic fungal pathogen that may cause pneumonia and lead to pulmonary fibrosis.

Aims

This study attempted to investigate the role of P. carinii infection-related genes in regulating lung fibrosis in mice.

Methods

A screening of P. carinii infection-related differential mRNAs was performed using the GEO database, followed by protein–protein interaction (PPI) network construction using the STRING website in order to obtain P. carinii infection-related key genes. The development of a mouse model with gene aberrant expression was achieved by utilizing mice carrying the Cre-LoxP recombinase system. Dexamethasone was employed to induce tracheal infection in order to develop a model of pulmonary fibrosis, and the magnitude of lung injury was assessed by performing hematoxylin–eosin (H&E) staining and Masson staining. Lung coefficient and hydroxyproline level were assessed on sections of lung tissue as well. Finally, the magnitude of lung fibrosis and inflammation in mice was determined based on immunofluorescence and on the expression of genes associated with lung fibrosis and inflammation.

Results

Fn1 was found by PPI with the highest connectivity in the PPI network associated with immunity and inflammation. Besides, Fn1 was significantly highly expressed in P. carinii-infected mice samples. The P carinii pneumonia (PCP)+Fn1^fl/fl group had significantly higher lung coefficients, hydroxyproline levels and TNF-α, IL-6, IL-1β, IL-8 and NLRP3 expression levels, and significantly lower IL-10 expression levels. The results found in PCP+SPC-Cre:Fn1^fl/fl group were the opposite. The results of the pulmonary fibrosis level study showed that the PCP+Fn1^fl/fl group had the most intense H&E and Masson staining, and significantly higher expression levels of Col1A2, Col3A1 and α-SMA, which were lower in the PCP+SPC-Cre:Fn1^fl/fl group.

Conclusions

P. carinii infection may promote the upregulation of Fn1, which causes pulmonary fibrosis with an inflammatory response.

查看原文本刊更多论文

卡氏肺囊虫感染导致 Fn1 表达上调，从而引起肺纤维化和炎症反应。

背景：目的：本研究试图探讨卡氏肺囊虫感染相关基因在调控小鼠肺纤维化中的作用：方法：利用GEO数据库对卡氏痢疾杆菌感染相关的差异mRNA进行筛选，然后利用STRING网站构建蛋白-蛋白相互作用（PPI）网络，以获得卡氏痢疾杆菌感染相关的关键基因。利用携带 Cre-LoxP 重组酶系统的小鼠建立了基因异常表达的小鼠模型。利用地塞米松诱导气管感染以建立肺纤维化模型，并通过苏木精-伊红（H&E）染色和马森染色评估肺损伤的程度。此外，还对肺组织切片的肺系数和羟脯氨酸水平进行了评估。最后，根据免疫荧光以及肺纤维化和炎症相关基因的表达确定了小鼠肺纤维化和炎症的程度：结果：PPI发现，在与免疫和炎症相关的PPI网络中，Fn1的连接性最高。此外，Fn1在卡里茵肺炎感染小鼠样本中明显高表达。卡里茵肺炎（PCP）+Fn1fl/fl组的肺系数、羟脯氨酸水平、TNF-α、IL-6、IL-1β、IL-8和NLRP3表达水平明显升高，而IL-10表达水平明显降低。PCP+SPC-Cre:Fn1fl/fl组的结果则相反。肺纤维化水平研究结果显示，PCP+Fn1fl/fl组的H&E和Masson染色最浓，Col1A2、Col3A1和α-SMA的表达水平明显较高，而PCP+SPC-Cre:Fn1fl/fl组则较低：结论：卡氏杆菌感染可能会促进Fn1的上调，从而导致肺纤维化并伴有炎症反应。

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

Revista Iberoamericana De Micologia MYCOLOGY-

CiteScore

1.90

自引率

0.00%

发文量

审稿时长

81 days

期刊介绍： Revista Iberoamericana de Micología (Ibero-American Journal of Mycology) is the official journal of the Asociación Española de Micología, Asociación Venezolana de Micología and Asociación Argentina de Micología (The Spanish, Venezuelan, and Argentinian Mycology Associations). The Journal gives priority to publishing articles on studies associated with fungi and their pathogenic action on humans and animals, as well as any scientific studies on any aspect of mycology. The Journal also publishes, in Spanish and in English, original articles, reviews, mycology forums, editorials, special articles, notes, and letters to the editor, that have previously gone through a scientific peer review process.