Transcriptome analysis reveals a protective role of liver X receptor alpha against silica particle-induced experimental silicosis

被引：12

作者：

Yao, Wu ^{[1
]}

Yang, Peiyan ^{[1
]}

Qi, Yuanmeng ^{[1
]}

Jin, Luheng ^{[1
]}

Zhao, Ahui ^{[1
]}

Ding, Mingcui ^{[1
]}

Wang, Di ^{[1
]}

Li, YiPing ^{[1
]}

Hao, Changfu ^{[1
]}

机构：

[1] Zhengzhou Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Zhengzhou 450001, Henan, Peoples R China

来源：

SCIENCE OF THE TOTAL ENVIRONMENT | 2020年 / 747卷

关键词：

Silica particles; Pulmonary fibroblasts; Fibrosis; LXR alpha; Silicosis; LUNG; BETA; INHIBITION; MODULATION; EXPRESSION; FIBROSIS; DISEASE;

D O I：

10.1016/j.scitotenv.2020.141531

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Silicosis, a severe and irreversible form of pulmonary fibrosis (PF) caused by long-termexposure to dust particles in production environments, is the biggest occupational health concern in China and most low-income countries. The transdifferentiation of pulmonary fibroblasts is the terminal event in silicosis, and specific transcription factors (TFs) play a crucial role in this condition. However, the relationship between TF-mediated regulation and silicosis remains unknown. We performed a transcriptomic analysis to elucidate this relationship, and our results revealed that two TFs, EGR2 and BHLHE40, were upregulated and five, i.e., TBX2, NR1H3 (LXR alpha), NR2F1, PPARG (PPAR gamma), and EPAS1, were downregulated in activated fibroblasts. Notably, PPAR gamma and LXR alpha expression was also decreased in an experimental mouse model of silicosis. The mechanism underlying these changes may involve TGF-beta 1 secretion from silica-exposed alveolar macrophages, causing PPAR gamma and LXR alpha downregulation, which in turn would result in aberrant alpha-SMA transcription. Our results suggest that LXR alpha is a potential target for the prevention of silicosis and PF. (C) 2020 Elsevier B.V. All rights reserved.

引用

页数：11

共 47 条

[1] Abduction and asylum in the lives of transcription factors [J].

Burger, Anat ;

Walczak, Aleksandra M. ;

Wolynes, Peter G. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (09) :4016-4021

[2] Developmental pathways in the pathogenesis of lung fibrosis [J].

Chanda, Diptiman ;

Otoupalova, Eva ;

Smith, Samuel R. ;

Volckaert, Thomas ;

De Langhe, Stijn P. ;

Thannickal, Victor J. .

MOLECULAR ASPECTS OF MEDICINE, 2019, 65 :56-69

[3] SiO2-induced release of sVEGFRs from pulmonary macrophages [J].

Chao, Jie ;

Lv, Yan ;

Chen, Jin ;

Wang, Jing ;

Yao, Honghong .

RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 2018, 247 :1-8

[4] TBtools: An Integrative Toolkit Developed for Interactive Analyses of Big Biological Data [J].

Chen, Chengjie ;

Chen, Hao ;

Zhang, Yi ;

Thomas, Hannah R. ;

Frank, Margaret H. ;

He, Yehua ;

Xia, Rui .

MOLECULAR PLANT, 2020, 13 (08) :1194-1202

[5] Chinese 1 strain of Toxoplasma gondii excreted-secreted antigens negatively modulate Foxp3 via inhibition of the TGFßRII/Smad2/Smad3/Smad4 pathway [J].

Chen, Jinling ;

Huang, Caiqun ;

Zhu, Dandan ;

Shen, Pei ;

Duan, Yinong ;

Wang, Jianxin ;

Yang, Chunzhao ;

Wu, Liting .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2017, 21 (09) :1944-1953

[6] Dioscin Alleviates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis through Promoting Alveolar Macrophage Autophagy [J].

Du, Sitong ;

Li, Chao ;

Lu, Yiping ;

Lei, Xue ;

Zhang, Yiting ;

Li, Siyi ;

Liu, Fangwei ;

Chen, Ying ;

Weng, Dong ;

Chen, Jie .

THERANOSTICS, 2019, 9 (07) :1878-1892

[7] Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis [J].

El Agha, Elie ;

Moiseenko, Alena ;

Kheirollahi, Vahid ;

De langhe, Stijn ;

Crnkovic, Slaven ;

Kwapiszewska, Grazyna ;

Kosanovic, Djuro ;

Schwind, Felix ;

Schermuly, Ralph T. ;

Henneke, Ingrid ;

MacKenzie, BreAnne ;

Quantius, Jennifer ;

Herold, Susanne ;

Ntokou, Aglaia ;

Ahlbrecht, Katrin ;

Morty, Rory E. ;

Guenther, Andreas ;

Seeger, Werner ;

Bellusci, Saverio .

CELL STEM CELL, 2017, 20 (02) :261-+

[8] The Early Growth Response Gene Egr2 (Alias Krox20) Is a Novel Transcriptional Target of Transforming Growth Factor-β that Is Up-Regulated in Systemic Sclerosis and Mediates Profibrotic Responses [J].

Fang, Feng ;

Ooka, Kohtaro ;

Bhattachyya, Swati ;

Wei, Jun ;

Wu, Minghua ;

Du, Pan ;

Lin, Simon ;

Del Galdo, Francesco ;

Feghali-Bostwick, Carol A. ;

Varga, John .

AMERICAN JOURNAL OF PATHOLOGY, 2011, 178 (05) :2077-2090

[9] Guidelines for the Diagnosis and Monitoring of Silicosis [J].

Fernandez Alvarez, Ramon ;

Martinez Gonzalez, Cristina ;

Quero Martinez, Aida ;

Blanco Perez, Jose Jestis ;

Carazo Fernandez, Luis ;

Prieto Fernandez, Amador .

ARCHIVOS DE BRONCONEUMOLOGIA, 2015, 51 (02) :86-93

[10] Targeting Bile Acid Receptors: Discovery of a Potent and Selective Farnesoid X Receptor Agonist as a New Lead in the Pharmacological Approach to Liver Diseases [J].

Festa, Carmen ;

De Marino, Simona ;

Carino, Adriana ;

Sepe, Valentina ;

Marchiano, Silvia ;

Cipriani, Sabrina ;

Di Leva, Francesco S. ;

Limongelli, Vittorio ;

Monti, Maria C. ;

Capolupo, Angela ;

Distrutti, Eleonora ;

Fiorucci, Stefano ;

Zampella, Angela .

FRONTIERS IN PHARMACOLOGY, 2017, 8

← 1 2 3 4 5 →