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Iron regulatory protein 2 (IRP2) deficiency is protective against resistive breathing-induced pulmonary inflammation

ABSTRACT: Iron regulatory protein 2 (IRP2), a post-transcriptional regulator of cellular iron metabolism has been associated with susceptibility to chronic obstructive pulmonary disease (COPD). To characterize the role of IRP2 in COPD pathogenesis, wild type and Irp2-/- mice were subjected to resistive breathing (RB) via tracheal banding. This experimental model recapitulates the mechanical stress and inflammation in the lungs observed during COPD exacerbations. RB promoted an increase in tissue elasticity and hysteresis in wild type but not in Irp2-/- mice, denoting that the latter were protected against lung injury. Moreover, Irp2-/- mice exhibited a lower score of lung inflammation. Additionally, only wild type but not Irp2-/- mice responded to RB by increasing bronchoalveolar lavage (BAL) cellularity due to higher macrophage count, which was accompanied by elevated BAL IL-1β and IL-6 levels. Lung proteomics and functional enrichment analysis revealed significant differences among wild type and Irp2-/- mice in RB-induced regulation of proteins involved in inflammatory and defense response pathways, but also of many proteins with unknown function. We conclude that IRP2 supports pro-inflammatory activities, while its deficiency protects against RB-induced pulmonary inflammation via remodeling of the lung proteome. Our data suggest that IRP2 is a bona fide pharmacological target against COPD.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

DISEASE(S): Chronic Obstructive Pulmonary Disease

SUBMITTER: Vincent Richard

LAB HEAD: Christoph Borchers

PROVIDER: PXD051589 | Pride | 2025-12-15

REPOSITORIES: Pride

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			Action	DRS
	EV001133_VR_SCPC_039_04_mouse_lung_1_221116204712.raw	Raw
	EV001134_VR_SCPC_039_04_mouse_lung_2.raw	Raw
	EV001135_VR_SCPC_039_04_mouse_lung_3.raw	Raw
	EV001136_VR_SCPC_039_04_mouse_lung_4.raw	Raw
	EV001137_VR_SCPC_039_04_mouse_lung_5.raw	Raw

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Iron regulatory protein 2 (IRP2) deficiency is protective against resistive breathing-induced pulmonary inflammation

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