Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 285, Issue 5, Pages L1147-L1152Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00098.2003
Keywords
developmental arteries and neural crest epidermal growth factor-like; elastase; interferon-gamma; interleukin-1 beta
Categories
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL066547, P01HL046902, P01HL047049] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL-66547, P01 HL-47049, P01 HL-46902] Funding Source: Medline
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Fibulin-5, previously known as DANCE and EVEC, is a secreted extracellular matrix protein that functions as a scaffold for elastin fiber assembly and as a ligand for integrins alpha(v)beta(3), alpha(v)beta(5), and alpha(9)beta(1). Fibulin-5 is developmentally regulated in the lung, and lung air space enlargement develops in mice deficient in fibulin-5. Fibulin-5 is also induced in adult lung following lung injury by hyperoxia. To further examine the role of fibulin-5 during repair of lung injury, we assessed fibulin-5 expression during elastase-induced emphysema in C57/b mice. Mice were treated with either saline or elastase via the trachea, and the lung was examined 20 days after treatment. Fibulin-5 mRNA was induced almost fourfold, whereas elastin mRNA was minimally elevated. Immunohistochemistry studies showed that fibulin-5 was induced in cells within the alveolar wall following elastase treatment. Western analysis demonstrates that fibulin-5 was strongly expressed in isolated primary lung interstitial fibroblasts. Fibulin-5 protein was localized to the fibroblast cell layer in culture, and brief elastase treatment degraded the protein. Intact fibulin-5 did not accumulate in the culture media. Treatment of fibroblasts with the proinflammatory cytokine interleukin-1beta abolished fibulin-5 mRNA expression. Our results indicate that fibulin-5 is coordinately expressed and regulated with elastin in lung fibroblasts and may serve a key role during lung injury and repair.
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