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Issue 6, 2016
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MicroRNA-338-5p modulates pulmonary hypertension-like injuries caused by SO2, NO2 and PM2.5 co-exposure through targeting the HIF-1α/Fhl-1 pathway

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Abstract

The role of ambient air pollution is considered to be important in the development of chronic obstructive pulmonary disease (COPD), and pulmonary hypertension (PH) is a common clinical manifestation of COPD. However, many studies have mainly focused on the adverse health effects of a single air pollutant, ignoring the combined toxicity of multiple pollutants. In the present study, we co-exposed mice to coal-burning air pollutants (SO2, NO2 and PM2.5), and confirmed PH-like injury occurrence by airflow limitation, marked abnormal endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) expression, and histopathological and ultrastructural alteration. Global microRNA (miRNA) arrays identified three significantly changed miRNAs homologous with humans (miR-338-5p, miR-450b-3p and miR-142-5p), and we targeted miR-338-5p based on real-time reverse transcription-PCR (RT-PCR) validation. Furthermore, bioinformatic and dual-luciferase reporter gene analyses indicated that miR-338-5p bound to 3′-UTR of hypoxia-inducible factor 1α (HIF-1α) mRNA and down-regulation of miR-338-5p led to the increased expression of HIF-1α and its related gene four-and-a-half LIM (Lin-11, Isl-1 and Mec-3) domain 1 (Fhl-1) and contributed to PH. This study provides evidence for the role of miRNAs in PH through targeting HIF-1α/Fhl-1 pathway after air pollutants co-exposure and implies new insights into the molecular markers for COPD caused by air pollution.

Graphical abstract: MicroRNA-338-5p modulates pulmonary hypertension-like injuries caused by SO2, NO2 and PM2.5 co-exposure through targeting the HIF-1α/Fhl-1 pathway

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Publication details

The article was received on 12 Jun 2016, accepted on 06 Sep 2016 and first published on 09 Sep 2016


Article type: Paper
DOI: 10.1039/C6TX00257A
Citation: Toxicol. Res., 2016,5, 1548-1560
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    MicroRNA-338-5p modulates pulmonary hypertension-like injuries caused by SO2, NO2 and PM2.5 co-exposure through targeting the HIF-1α/Fhl-1 pathway

    X. Ji, Y. Zhang, T. Ku, Y. Yun, G. Li and N. Sang, Toxicol. Res., 2016, 5, 1548
    DOI: 10.1039/C6TX00257A

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