Aging Delays Lung Repair: Insights from Omics Analysis in Mice with Pulmonary Fibrosis

Liang, Jiurong; Ligresti, Giovanni

doi:10.1165/rcmb.2023-0171ed

Cited by 4 publications

(2 citation statements)

References 15 publications

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“…However, based on our normalized gene expressions of collagen, lysyl oxidase, and proteases, older mice did not show significant dysregulation levels than younger mice in most fibrotic markers. It has been reported that the bleomycin-induced fibrosis model serves better in the old mice, in which the chronological aging could delay fibroblast-dominated repair capacity, hence inducing persistent scarring and ECM deposition, whereas young mice showed recovery in lung scarring [ 55 , 56 ]. Bleomycin treatment for 14 days might not be enough for mimicking the fibrogenesis progression in humans since it is a chronic lung disease.…”

Section: Discussionmentioning

confidence: 99%

Environmental tobacco smoke exposure exaggerates bleomycin-induced collagen overexpression during pulmonary fibrogenesis

Wang,

Goracci,

Sundar

et al. 2024

J Inflamm

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Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism that ETS exposure augments pulmonary fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation. C57BL/6J and p16-3MR mice were exposed to ETS followed by bleomycin administration. ETS exposure exacerbated bleomycin-induced collagen and lysyl oxidase overexpression in the fibrotic lesion. ETS exposure also led to augmented bleomycin-induced upregulation of C3 and C3AR, which are pro-fibrotic markers. Moreover, overexpressed collagens and C3 levels were highly significant in males than females. The old mice (17 months old) were exposed to ETS and treated with bleomycin to induce fibrogenesis which is considered as an aging-associated disease. Fewer gene and protein dysregulations trends were identified between ETS exposure with the bleomycin group and the bleomycin alone group in old mice. Based on our findings, we suggested that ETS exposure increases the risk of developing severe lung fibrotic responses via collagen overexpression and lysyl oxidase-mediated collagen stabilization in the fibrotic lesion, and potentially affected the complement system activation induced by bleomycin. Further, male mice were more susceptible than females during fibrogenesis exacerbation. Thus ETS and bleomycin induced lung fibrotic changes via collagen-lysyl oxidase in an age-dependent mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Environmental tobacco smoke exposure exaggerates bleomycin-induced collagen overexpression during pulmonary fibrogenesis

Wang,

Goracci,

Sundar

et al. 2024

J Inflamm

View full text Add to dashboard Cite

show abstract

“…However, based on our normalized gene expressions of collagen, lysyl oxidase, and proteases, older mice did not show significant dysregulation levels than younger mice in most fibrotic markers. It has been reported that the bleomycin-induced fibrosis model serves better in the old mice, in which the chronological aging could delay fibroblast-dominated repair capacity, hence inducing persistent scarring and ECM deposition, whereas young mice showed recovery in lung scarring ( 50 , 51 ). Bleomycin treatment for 14 days might not be enough for mimicking the fibrogenesis progression in humans since it is a chronic lung disease.…”

Section: Discussionmentioning

confidence: 99%

Environmental tobacco smoke exposure exaggerates bleomycin- induced collagen overexpression during pulmonary fibrogenesis

Wang,

Goracci,

Sundar

et al. 2023

Preprint

View full text Add to dashboard Cite

Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism by which ETS exposure augments lung fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation. C57BL/6J and p16-3MR mice were exposed to ETS followed by bleomycin administration. ETS exposure exacerbated bleomycin-induced collagen and lysyl oxidase overexpression in the fibrotic lesion. ETS exposure also led to augmented bleomycin-induced upregulation of C3 and C3AR, which are pro-fibrotic markers. Moreover, overexpressed collagens and C3 levels were highly significant in males than females. The old mice (17 months old) were exposed to ETS and treated with bleomycin to induce fibrogenesis, since fibrogenesis is an aging-associated disease. Fewer gene and protein dysregulations trends were identified between ETS exposure with the bleomycin group and the bleomycin alone group in old mice. Based on our findings, we suggested that ETS exposure increases the risk of developing severe lung fibrotic responses via collagen overexpression and lysyl oxidase-mediated collagen stabilization in the fibrotic lesion. ETS exposure also potentially affected the complement system activation induced by bleomycin. Further, male mice were more susceptible than females during fibrogenesis exacerbation.

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Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility to Pulmonary Fibrosis

Xu,

Ding,

et al. 2024

The American Journal of Pathology

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Aging Delays Lung Repair: Insights from Omics Analysis in Mice with Pulmonary Fibrosis

Cited by 4 publications

References 15 publications

Environmental tobacco smoke exposure exaggerates bleomycin-induced collagen overexpression during pulmonary fibrogenesis

Environmental tobacco smoke exposure exaggerates bleomycin-induced collagen overexpression during pulmonary fibrogenesis

Environmental tobacco smoke exposure exaggerates bleomycin- induced collagen overexpression during pulmonary fibrogenesis

Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility to Pulmonary Fibrosis

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