Collagen metabolism in experimental lung silicosis. A trimodal behavior of collagenolysis

Ramos, Carlos; Montaño, Martha; González, Gabriel Alcántar; Vadillo, Felipe; Selman, Moisés

doi:10.1007/bf02714067

Cited by 15 publications

(8 citation statements)

References 13 publications

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“…Indeed, these results confirm older findings suggesting that early fibrogenesis is characterized by an increase in collagen synthesis as well as collagenase activity, whereas in more advanced stages a progressive decrease in collagenolytic activity is usually observed (2,34). The findings of the present study suggest that this process is at least partially associated with changes in collagenase expression, which is markedly increased in early stages whereas it shows a concomitant decrease in late stages.…”

Section: Discussionsupporting

confidence: 92%

“…The disease has been reproduced in several animal models, which develop morphologic changes similar to the human disorder (2,3). Silica-induced granulomatous inflammation is characterized by accumulations of macrophages and lymphocytes with mineral particles in the nodules.…”

mentioning

confidence: 97%

“…Previous work has found evidence of increased collagen expression and synthesis (2,4) but research on the breakdown pathway is scanty.…”

mentioning

confidence: 98%

“…Silica-induced granulomatous inflammation is characterized by accumulations of macrophages and lymphocytes with mineral particles in the nodules. The inflammatory reaction is followed by a fibrotic response with fibroblast proliferation and excessive extracellular matrix accumulation, including interstitial collagens and insoluble elastin (2,4,5). However, the mechanisms responsible of the pathological alterations leading to the fibrotic response in the silicotic nodules are far from being elucidated.…”

mentioning

confidence: 99%

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Matrix Metalloproteinases 2, 9, and 13, and Tissue Inhibitors of Metalloproteinases 1 and 2 in Experimental Lung Silicosis

Pérez‐Ramos

Segura-Valdez

Cantón

et al. 1999

Am J Respir Crit Care Med

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Exposure to silica induces granulomatous lung inflammation evolving to fibrosis through yet unclear pathogenic mechanisms. We examined the expression of extracellular matrix remodeling molecules: collagenase 3, gelatinases A and B, and TIMP-1 and TIMP-2 in experimental lung silicosis. Rats were instilled with 50 mg of silica and sacrificed after 15 and 60 d. At 60 d a significant increase in lung collagen content was found (170.2 +/- 34.4 versus 88.2 +/- 20.8 microgram/mg in controls, p = 0.01). Gelatin zymography of bronchoalveolar lavage fluid (BALF) from 15 and 60 d revealed bands of progelatinase A and progelatinase B, and lung tissue zymograms showed in addition, the active gelatinase A form at 15 d. By in situ hybridization and immunohistochemistry, early silicotic granulomas exhibited intense staining for all matrix metalloproteinases (MMPs) and TIMPs assayed. Labeling was restricted inside granulomas and surrounding areas. Late silicotic granulomas at 60 d showed lower MMP expression than did early lesions, and in highly fibrotic nodules scarce signal was usually found. TIMP-1 and TIMP-2 showed a moderate reduction in 60-d silicotic nodules. These findings suggest that an imbalance in the expression of MMPs and TIMPs may be implicated in extracellular matrix remodeling and basement membrane disruption during experimental lung silicosis.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 97%

“…Previous work has found evidence of increased collagen expression and synthesis (2,4) but research on the breakdown pathway is scanty.…”

mentioning

confidence: 98%

mentioning

confidence: 99%

See 2 more Smart Citations

Matrix Metalloproteinases 2, 9, and 13, and Tissue Inhibitors of Metalloproteinases 1 and 2 in Experimental Lung Silicosis

Pérez‐Ramos

Segura-Valdez

Cantón

et al. 1999

Am J Respir Crit Care Med

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“…The overall goal for the present research was to employ lucifer yellow stain and confocal microscopy to quantitate the extent of pulmonary übrosis in lung tissue sections. We pursed this goal by examining tissues from a wellcharacterized animal model of pulmonary übrosis, silicosis in the mouse [3][4][5][6][7][8][9][10][11][12][13].…”

mentioning

confidence: 99%

Quantitative Image Analysis of Lung Connective Tissue in Murine Silicosis

Antonini

Hemenway

Davis

2000

Experimental Lung Research

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Pulmonary fibrosis is a disabling consequence of many lung diseases but is difficult to quantify. Lucifer yellow CH fluorescent dye (LY) appears to stain connective tissue matrix macromolecules selectively. Laser scanning confocal microscopy can quantify the intensity of fluorescence and determine the area of fluorescent material. We hypothesized that the abundance of lucifer yellow-stained matrix macromolecules in lung tissue sections could be measured by laser scanning confocal microscopy, would reflect differences between varying degrees of pulmonary fibrosis, and could be compared directly to biochemical measurements of lung collagen. We exposed C57B1/6 and 129 strains of mice by aerosol to cristobalite silica (70 mg/m3, 12 days, 5 hours/day) or sham-air and examined them 2 and 16 weeks after exposure. The area of LY-stained matrix in tissue sections was quantitated by laser scanning confocal microscopy, and total lung collagen was measured biochemically as hydroxyproline (OH-proline). The LY-stained connective tissue matrix appeared as bright linear bands in the alveolar septae, and was increased significantly by image analysis in C57B1/6 and 129 mice with silicosis 16 weeks after exposure. Total lung OH-proline was significantly increased in silica-exposed mice from both stains at both time points. Comparing all 8 groups, there was a significant linear correlation between the average area of connective tissue measured by LY stain and the total OH-proline per lung measured by chemical analysis (r = .72, P = .042). LY staining and confocal microscopy with image analysis offers a rapid technique for quantitative measurements of the extent of pulmonary fibrosis.

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