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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.

No MeSH data available.


Related in: MedlinePlus

MMP and TIMP-1 protein expression levels in tissue samples from the 125 day asthma experimental model. (A) MMP-1 was observed as a 56-kDa band in all samples assayed. Pro-MMP-13 and MMP-13 active forms were visualized in all groups. TIMP-1 (28-kDa band) as well as TIMP-1 polymers and complexes were also identified in all samples, particularly in group III animals. (B) A significant increase in MMP-1 expression levels was observed in tissue samples from group II, as compared with control animals (*P=0.03). MMP-13 expression levels were similar in tissue samples from the 3 groups. TIMP-1 protein expression levels in group II tissue samples were significantly increased, as compared with group I (**P=0.02). Bars indicate the mean ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.
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f7-etm-0-0-3509: MMP and TIMP-1 protein expression levels in tissue samples from the 125 day asthma experimental model. (A) MMP-1 was observed as a 56-kDa band in all samples assayed. Pro-MMP-13 and MMP-13 active forms were visualized in all groups. TIMP-1 (28-kDa band) as well as TIMP-1 polymers and complexes were also identified in all samples, particularly in group III animals. (B) A significant increase in MMP-1 expression levels was observed in tissue samples from group II, as compared with control animals (*P=0.03). MMP-13 expression levels were similar in tissue samples from the 3 groups. TIMP-1 protein expression levels in group II tissue samples were significantly increased, as compared with group I (**P=0.02). Bars indicate the mean ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.

Mentions: Immunoblotting assay demonstrated the presence of MMP-1 as a band of 56-kDa (active form) in the tissue samples of animals from all 3 groups (Fig. 7A). MMP-1 expression levels were significantly higher in group II tissue samples, as compared with tissue samples obtained from the control animals (95,204.3±4,677.2 and 48,351±4,920.6 DU, respectively; P=0.03), but not with group III tissue samples (55,058.7±5,196.5 DU; Fig. 7B).


Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma
MMP and TIMP-1 protein expression levels in tissue samples from the 125 day asthma experimental model. (A) MMP-1 was observed as a 56-kDa band in all samples assayed. Pro-MMP-13 and MMP-13 active forms were visualized in all groups. TIMP-1 (28-kDa band) as well as TIMP-1 polymers and complexes were also identified in all samples, particularly in group III animals. (B) A significant increase in MMP-1 expression levels was observed in tissue samples from group II, as compared with control animals (*P=0.03). MMP-13 expression levels were similar in tissue samples from the 3 groups. TIMP-1 protein expression levels in group II tissue samples were significantly increased, as compared with group I (**P=0.02). Bars indicate the mean ± 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

f7-etm-0-0-3509: MMP and TIMP-1 protein expression levels in tissue samples from the 125 day asthma experimental model. (A) MMP-1 was observed as a 56-kDa band in all samples assayed. Pro-MMP-13 and MMP-13 active forms were visualized in all groups. TIMP-1 (28-kDa band) as well as TIMP-1 polymers and complexes were also identified in all samples, particularly in group III animals. (B) A significant increase in MMP-1 expression levels was observed in tissue samples from group II, as compared with control animals (*P=0.03). MMP-13 expression levels were similar in tissue samples from the 3 groups. TIMP-1 protein expression levels in group II tissue samples were significantly increased, as compared with group I (**P=0.02). Bars indicate the mean ± standard error. MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase.
Mentions: Immunoblotting assay demonstrated the presence of MMP-1 as a band of 56-kDa (active form) in the tissue samples of animals from all 3 groups (Fig. 7A). MMP-1 expression levels were significantly higher in group II tissue samples, as compared with tissue samples obtained from the control animals (95,204.3±4,677.2 and 48,351±4,920.6 DU, respectively; P=0.03), but not with group III tissue samples (55,058.7±5,196.5 DU; Fig. 7B).

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