Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr;46(2):763-778.
doi: 10.1007/s10753-022-01772-4. Epub 2022 Dec 29.

IRAK-M Regulates Proliferative and Invasive Phenotypes of Lung Fibroblasts

Zhoude Zheng  1 , Jia Li  1 , Ye Cui  2 , Wei Wang  2 , Mingqiang Zhang  1   3 , Youming Zhang  4 , Yan Bai  5 , Sun Ying  2 , Jinming Gao  6
Affiliations

IRAK-M Regulates Proliferative and Invasive Phenotypes of Lung Fibroblasts

Zhoude Zheng et al. Inflammation. 2023 Apr.

Abstract

Lung fibroblasts play an important role in subepithelial fibrosis, one feature for airway remodeling. IL-1 receptor-associated kinase (IRAK)-M was shown to involve fibrosis formation in airways and lung through regulation of inflammatory responses. IRAK-M is expressed by lung fibroblasts, whether IRAK-M has direct impact on lung fibroblasts remains unclear. In this investigation, we evaluated in vitro effect of IRAK-M on phenotypes of lung fibroblasts by silencing or overexpressing IRAK-M. Murine lung fibroblasts (MLg) were stimulated with house dust mite (HDM), IL-33, and transforming growth factor (TGF) β1. Techniques of small interfering RNA or expression plasmid were employed to silence or overexpress IRAK-M in MLg fibroblast cells. Proliferation, migration, invasiveness, and fibrosis-related events were evaluated. Significant upregulation of IRAK-M expression in MLg cells was caused by these stimuli. Silencing IRAK-M significantly increased proliferation, migration, and invasiveness of lung fibroblasts regardless of stimulating conditions. By contrast, IRAK-M overexpression significantly inhibited proliferation and motility of MLg lung fibroblasts. IRAK-M overexpression also significantly decreased the expression of fibronectin, collagen I, and α-SMA in MLg cells. Under stimulation with TGFβ1 or IL-33, IRAK-M silencing reduced MMP9 production, while IRAK-M overexpression increased MMP9 production. Modulation of IRAK-M expression affected cytokines production, either decreased or increased expression of TNFα and CXCL10 by the cells regardless of stimulation. Our in vitro data reveal that IRAK-M directly impacts on lung fibroblasts through modulation of cellular motility, release of inflammatory, and fibrotic cytokines of lung fibroblasts. These might suggest a new _target by regulation of IRAK-M in slowing airway remodeling.

Keywords: IRAK-M; airway remodeling; asthma.; fibroblast; fibroblast invasiveness.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Prakash, Y.S., A.J. Halayko, R. Gosens, R.A. Panettieri Jr., B. Camoretti-Mercado, R.B. Penn, and ATS Assembly on Respiratory Structure and Function. 2017. An official American Thoracic Society research statement: Current challenges facing research and therapeutic advances in airway remodeling. American Journal of Respiratory and Critical Care Medicine 195: e4–e19. - PubMed - DOI
    1. Elias, J.A., Z. Zhu, G. Chupp, and R.J. Homer. 1999. Airway remodeling in asthma. The Journal of Clinical Investigation 104: 1001–1006. - PubMed - PMC - DOI
    1. James, A.L., and S. Wenzel. 2007. Clinical relevance of airway remodelling in airway diseases. European Respiratory Journal 30: 134–155. - PubMed - DOI
    1. Bumbacea, D., D. Campbell, L. Nguyen, D. Carr, P.J. Barnes, D. Robinson, and K.F. Chung. 2004. Parameters associated with persistent airflow obstruction in chronic severe asthma. European Respiratory Journal 24: 122–128. - PubMed - DOI
    1. Woodruff, P.G., B. Modrek, D.F. Choy, G. Jia, A.R. Abbas, A. Ellwanger, L.L. Koth, J.R. Arron, and J.V. Fahy. 2009. T-helper type 2-driven inflammation defines major subphenotypes of asthma. American Journal of Respiratory and Critical Care Medicine 180: 388–395. - PubMed - PMC - DOI

Substances

LinkOut - more resources

  NODES
INTERN 2
twitter 2