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Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma

View Article: PubMed Central - PubMed

ABSTRACT

Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models. A group of animals from either model was sacrificed 1 h or 1 month after the last OVA challenge. Collagen distribution, collagen content, interstitial collagenase activity and matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-1 protein expression levels were measured in the lung tissue samples from both experimental models. The results revealed that collagen deposit in bronchiole BM, adventitial and airway smooth muscle layers was increased in both experimental models as well as lung tissue collagen concentration. These structural changes persisted 1 month after the last OVA challenge. In the acute model, a decrease in collagenase activity and in MMP-1 concentration was observed. Collagenase activity returned to basal levels, and an increase in MMP-1 and MMP-13 expression levels along with a decrease in TIMP-1 expression levels were observed in animals sacrificed 1 month after the last OVA challenge. In the chronic model, there were no changes in collagenase activity or in MMP-13 concentration, although MMP-1 expression levels increased. One month later, an increase in collagenase activity was observed, although MMP-1 and TIMP-1 levels were not altered. The results of the present study suggest that even when the allergen challenges were discontinued, and collagenase activity and MMP-1 expression increased, fibrosis remained, contributing to the irreversibility of bronchoconstriction.

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Comparison of MMP and TIMP-1 tissue concentrations in the acute and chronic experimental models of asthma. (A) MMP-1 levels were significantly increased in group II from the chronic model (125 days), as compared with group II from the acute model (35 days; *P=0.05). MMP-1 levels were significantly higher in group III from the 35 days model than group III from the 125 days model (**P=0.02). (B) MMP-13 levels were significantly increased in group I and II from the acute model (35 days), as compared with the chronic model (125 days; *P=0.008 and **P=0.02, respectively). Conversely, MMP-13 levels were significantly increased in group III from the chronic model (125 days), as compared with group III from the acute model (35 days; ***P=0.02). (C) TIMP-1 concentration was significantly increased in the 3 groups from the chronic model (125 days), as compared with groups from the acute model (35 days; *P=0.03, **P=0.03 and ***P=0.008). Bars indicate means ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.
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f8-etm-0-0-3509: Comparison of MMP and TIMP-1 tissue concentrations in the acute and chronic experimental models of asthma. (A) MMP-1 levels were significantly increased in group II from the chronic model (125 days), as compared with group II from the acute model (35 days; *P=0.05). MMP-1 levels were significantly higher in group III from the 35 days model than group III from the 125 days model (**P=0.02). (B) MMP-13 levels were significantly increased in group I and II from the acute model (35 days), as compared with the chronic model (125 days; *P=0.008 and **P=0.02, respectively). Conversely, MMP-13 levels were significantly increased in group III from the chronic model (125 days), as compared with group III from the acute model (35 days; ***P=0.02). (C) TIMP-1 concentration was significantly increased in the 3 groups from the chronic model (125 days), as compared with groups from the acute model (35 days; *P=0.03, **P=0.03 and ***P=0.008). Bars indicate means ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.

Mentions: MMP-1 concentrations were significantly higher in group II from the 125 day model compared with group II from the 35 day model (95,204.3±4,677.2 and 49,325.3±3,319.9 DU, respectively; P=0.05; Fig. 8A). There were also significant differences in MMP-1 content between group III from the 35 day model and group III from the 125 day model (97,338.1±1,038.1 and 55,058.7±5,196.5 DU, respectively; P=0.02). There were no significant differences between groups I in either model.


Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma
Comparison of MMP and TIMP-1 tissue concentrations in the acute and chronic experimental models of asthma. (A) MMP-1 levels were significantly increased in group II from the chronic model (125 days), as compared with group II from the acute model (35 days; *P=0.05). MMP-1 levels were significantly higher in group III from the 35 days model than group III from the 125 days model (**P=0.02). (B) MMP-13 levels were significantly increased in group I and II from the acute model (35 days), as compared with the chronic model (125 days; *P=0.008 and **P=0.02, respectively). Conversely, MMP-13 levels were significantly increased in group III from the chronic model (125 days), as compared with group III from the acute model (35 days; ***P=0.02). (C) TIMP-1 concentration was significantly increased in the 3 groups from the chronic model (125 days), as compared with groups from the acute model (35 days; *P=0.03, **P=0.03 and ***P=0.008). Bars indicate means ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998200&req=5

f8-etm-0-0-3509: Comparison of MMP and TIMP-1 tissue concentrations in the acute and chronic experimental models of asthma. (A) MMP-1 levels were significantly increased in group II from the chronic model (125 days), as compared with group II from the acute model (35 days; *P=0.05). MMP-1 levels were significantly higher in group III from the 35 days model than group III from the 125 days model (**P=0.02). (B) MMP-13 levels were significantly increased in group I and II from the acute model (35 days), as compared with the chronic model (125 days; *P=0.008 and **P=0.02, respectively). Conversely, MMP-13 levels were significantly increased in group III from the chronic model (125 days), as compared with group III from the acute model (35 days; ***P=0.02). (C) TIMP-1 concentration was significantly increased in the 3 groups from the chronic model (125 days), as compared with groups from the acute model (35 days; *P=0.03, **P=0.03 and ***P=0.008). Bars indicate means ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.
Mentions: MMP-1 concentrations were significantly higher in group II from the 125 day model compared with group II from the 35 day model (95,204.3±4,677.2 and 49,325.3±3,319.9 DU, respectively; P=0.05; Fig. 8A). There were also significant differences in MMP-1 content between group III from the 35 day model and group III from the 125 day model (97,338.1±1,038.1 and 55,058.7±5,196.5 DU, respectively; P=0.02). There were no significant differences between groups I in either model.

View Article: PubMed Central - PubMed

ABSTRACT

Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models. A group of animals from either model was sacrificed 1 h or 1 month after the last OVA challenge. Collagen distribution, collagen content, interstitial collagenase activity and matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-1 protein expression levels were measured in the lung tissue samples from both experimental models. The results revealed that collagen deposit in bronchiole BM, adventitial and airway smooth muscle layers was increased in both experimental models as well as lung tissue collagen concentration. These structural changes persisted 1 month after the last OVA challenge. In the acute model, a decrease in collagenase activity and in MMP-1 concentration was observed. Collagenase activity returned to basal levels, and an increase in MMP-1 and MMP-13 expression levels along with a decrease in TIMP-1 expression levels were observed in animals sacrificed 1 month after the last OVA challenge. In the chronic model, there were no changes in collagenase activity or in MMP-13 concentration, although MMP-1 expression levels increased. One month later, an increase in collagenase activity was observed, although MMP-1 and TIMP-1 levels were not altered. The results of the present study suggest that even when the allergen challenges were discontinued, and collagenase activity and MMP-1 expression increased, fibrosis remained, contributing to the irreversibility of bronchoconstriction.

No MeSH data available.


Related in: MedlinePlus