Elevated circulating MMP-9 is linked to increased COPD exacerbation risk in SPIROMICS and COPDGene

Wells, James M.; Parker, Margaret M.; Oster, Robert A.; Bowler, R.P.; Dransfield, Mark T.; Bhatt, Surya P.; Cho, Michael H.; Kim, Victor; Curtis, Jeffrey L.; Martínez, Fernando J.; Paine, Robert; O’Neal, Wanda K.; Labaki, Wassim W.; Kaner, Robert J.; Barjaktarević, Igor; Han, MeiLan K.; Silverman, Edwin K.; Crapo, James D.; Barr, R. Graham; Woodruff, Prescott G.; Castaldi, Peter J.; Gaggar, Amit; Investigators, COPDGene

doi:10.1172/jci.insight.123614

Cited by 65 publications

(50 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The levels of MMP-9 in serum and exhaled breath condensate of COPD patients signi cantly increased [39,40]. Some scholars have considered the MMP-9 concentration and the MMP-9/TIMP-1 ratio are the best predictors for emphysema in COPD patients [41,42]. In T0901317 treated 6 week-group, the level of MMP9 was lower compared to the ozone exposure group.…”

Section: Discussionmentioning

confidence: 99%

liver X receptors inhibit pulmonary inflammation and airway remodeling induced by ozone exposure in mice

Yu¹,

Zheng²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Ozone (O3) exposure can lead to airway inflammation, hyperreactivity and airway remodeling. Liver X receptors (LXRs) play an important role in attenuating inflammation. The therapeutic effects of LXRs on ozone-induced pulmonary inflammation and airway remodeling were examined. C57/BL6 mice were exposed to ozone for 1 or 6 weeks. LXR agonist T0901317 was administered to mice at one hour before ozone exposure. As expected, ozone-exposed mice developed lung inflammation with augmented neutrophil, macrophage, TNF-α, IL-6, IL-8 and G-CSF in the bronchoalveolar lavage fluid and serum. The increase in MMP-9 and α-SMA expression, and collagen deposition around airway reflected the airway remodeling in ozone-exposed mice. Compared with ozone-exposed mice, LXR agonist T0901317 inhibited the ozone-induced inflammation after 1 and 6 weeks in the ozone exposure model. In addition, the treatment with the LXR agonist prevented alveolar enlargement and reduced airway remodeling in 6-week ozone-induced mice. Therefore, LXRs may repress pulmonary inflammation and attenuate the progression of airway remodeling.

show abstract

Section: Discussionmentioning

confidence: 99%

liver X receptors inhibit pulmonary inflammation and airway remodeling induced by ozone exposure in mice

Yu¹,

Zheng²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Consistent with previous reports (19,24,32), the serum concentration of MMP9 was signi cantly increased in the COPD group in our study. It has been proven that MMP9 was associated with pulmonary function and indicators of small airway disease in COPD (33,34).To further explore whether sestrin2 is related to airway remodeling in COPD, immunohistochemical staining in the airway was done and showed that there was a signi cantly higher expression of sestrin2 in the airway in the COPD group, especially in bronchial epithelial cells full of MMP9. Furthermore, we also found that the serum sestrin2 concentrations were positively correlated with serum MMP9 concentrations.…”

Section: Discussionmentioning

confidence: 99%

Sestrin2 Was Involved in Airway Remodeling in COPD: A Multi-level Research

Zhang¹,

Wei²,

Ji³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background. Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), which is greatly associated with oxidative stress. Sestrin2 has recently drawn attention as a representative antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has not yet been clarified.Methods. A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were showed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was assessed by Immunohistochemistry staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) of all participants were measured for the evaluation of airway remodeling. Serum sestrin2 concentrations' relationship with MMP9 and airway parameters on chest CT was further analyzed. Results. In patients with COPD, staining results of airway structure showed noticeable pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were found on chest CT. Additionally, the serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters on chest CT.Conclusion. Increased expression of sestrin2 is related to airway remodeling in COPD at three levels including histology, biomarkers and imaging. It is demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in COPD.

show abstract

“…Emphysema caused by lung instillation of porcine pancreatic elastase has been a disease model widely used in support of the protease-antiprotease imbalance [20]. Many studies found elevated MMPs concentration and increased elastin degradation in chronic obstructive pulmonary diseases [21][22][23]. Neutrophil elastase or matrix metalloproteinases (MMPs) were held culprit [24].…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosainduced acute emphysema through bacterial secretion in mice

Zhu

Pan

2020

Preprint

View full text Add to dashboard Cite

Pulmonary emphysema is the major pathological feature of chronic obstructive pulmonary disease (COPD). It is a slowly progressive pathological condition and acute lung infection is not considered to play a role in emphysema initiation. Recently, we found that the secretion from Pseudomonas aeruginosa could cause severe lung emphysema in mice rapidly. Since this bacterium is ubiquitous and secrets proteases, we hypothesized that direct P. aeruginosa airway infection would have a similar effect. To address this issue, we applied a unilateral lung injury model. P. aeruginosa secretion was extracted and instilled intratracheally into the left lung of C57BL/6 and C3H/HeJ mice, while the right lung was saved as self-control. Alveolar diameter and lung compliance were measured. Later, we tested the effect of P. aeruginosa inoculation in C57BL/6 mice, immunosuppressed C57BL/6 mice, and C3H/HeJ (TLR4 deficient) mice. P. aeruginosa secretion extract caused acute panacinar emphysema and decreased dynamic lung compliance. Different types of emphysema are transformable. However, the P. aeruginosa infection could only elicit emphysema in C3H/HeJ mice and immunosuppressed C57BL/6 mice, indicating normal immunity is essential to protect the hosts from emphysema. P. aeruginosa could be an important pathogen in COPD initiation. Our finding filled a major gap in COPD pathogenesis.

show abstract

Elevated circulating MMP-9 is linked to increased COPD exacerbation risk in SPIROMICS and COPDGene

Cited by 65 publications

References 34 publications

liver X receptors inhibit pulmonary inflammation and airway remodeling induced by ozone exposure in mice

liver X receptors inhibit pulmonary inflammation and airway remodeling induced by ozone exposure in mice

Sestrin2 Was Involved in Airway Remodeling in COPD: A Multi-level Research

Pseudomonas aeruginosainduced acute emphysema through bacterial secretion in mice

Contact Info

Product

Resources

About