Collagen-related gene and protein expression changes in the lung in response to chronic hypoxia |
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Authors: | Kristine D Estrada Naomi C Chesler |
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Institution: | (1) Biomedical Engineering Department, University of Wisconsin, Madison, 2146 Engineering Centers Building, 1550 Engineering Drive, Madison, WI 53706-1609, USA |
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Abstract: | Collagen accumulation likely contributes to increased vascular and airway impedance in hypoxia-induced pulmonary hypertension
(HPH). Collagen exists in multiple subtypes and can accumulate via increased synthesis or decreased degradation. To better
understand the individual contributions of fibrillar (FB) and basement membrane (BM) collagen, matrix metalloproteinases (MMPs)
and tissue inhibitors of MMPs (TIMPs) to pulmonary vascular and airway remodeling in HPH, we investigated the temporal changes
in gene and protein expression in the lungs of mice exposed to hypoxia for 0, 3, 6, 10 and 15 days. The earliest and largest
change in gene expression was of type I FB collagen, which was significantly increased over control levels at 6, 10 and 15
days of hypoxia (p < 0.05). Type III FB and type IV BM collagen were increased at 10 and 15 days of hypoxia (p < 0.05); MMP and TIMP gene expression levels were typically higher but sometimes lower than control levels at various time
points. Collagen protein content was increased in whole lungs as early as 6 days of hypoxia and increased monotonically with
longer exposures. However, neither qualitative nor semi-quantitative analysis of immunohistochemistry demonstrated accumulation
of type I FB collagen in compartments of the lung other than large airways, suggesting that other collagen subtypes may be
important contributors to collagen protein accumulation. These results provide insight into the patterns of gene and protein
expression relevant to collagen accumulation in the lung in response to chronic hypoxia, through which we can develop a better
understanding of the time course of changes in matrix biology and biomechanics that occur in HPH. |
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Keywords: | Extracellular matrix Pulmonary vascular remodeling Airway remodeling Hypoxia-induced pulmonary hypertension |
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