- Title
- Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma
- Creator
- Tu, Xiaofan; Gomez, Henry M.; Donovan, Chantal; Kim, Richard Y.; Brown, Alexandra C.; de Jong, Emma; Galvao, Izabela; Faiz, Alen; Bosco, Anthony; Horvat, Jay C.; Hansbro, Philip
- Relation
- NHMRC.1120152 http://purl.org/au-research/grants/nhmrc/1120152 | 1138402 http://purl.org/au-research/grants/nhmrc/1138402
- Relation
- Respiratory Research Vol. 24, Issue 1, no. 32
- Publisher Link
- http://dx.doi.org/10.1186/s12931-022-02298-x
- Publisher
- BioMed Central Ltd.
- Resource Type
- journal article
- Date
- 2023
- Description
- Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma in disease pathogenesis may expedite the development of novel targeted treatment strategies. In this study, we performed transcriptomics on the airway and parenchyma using a house dust mite (HDM)-induced model of experimental asthma that replicates key features of the human disease. HDM exposure increased the expression of 3,255 genes, of which 212 were uniquely increased in the airways, 856 uniquely increased in the parenchyma, and 2187 commonly increased in both compartments. Further interrogation of these genes using a combination of network and transcription factor enrichment analyses identified several transcription factors that regulate airway and/or parenchymal gene expression, including transcription factor EC (TFEC), transcription factor PU.1 (SPI1), H2.0-like homeobox (HLX), metal response element binding transcription factor-1 (MTF1) and E74-like factor 4 (ets domain transcription factor, ELF4) involved in controlling innate immune responses. We next assessed the effects of inhibiting lung SPI1 responses using commercially available DB1976 and DB2313 on key disease outcomes. We found that both compounds had no protective effects on airway inflammation, however DB2313 (8 mg/kg) decreased mucus secreting cell number, and both DB2313 (1 mg/kg) and DB1976 (2.5 mg/kg and 1 mg/kg) reduced small airway collagen deposition. Significantly, both compounds decreased airway hyperresponsiveness. This study demonstrates that SPI1 is important in HDM-induced experimental asthma and that its pharmacological inhibition reduces HDM-induced airway collagen deposition and hyperresponsiveness.
- Subject
- house dust mite; asthma; remodeling; AHR; transcriptomics; SPI1; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1480253
- Identifier
- uon:50469
- Identifier
- ISSN:1465-9921
- Rights
- © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Language
- eng
- Full Text
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