Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair.
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 alphavbeta3, alphavbeta5, and alpha9beta1. 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.
Kuang
Ping-Ping
PP
The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Goldstein
Ronald H
RH
Liu
Yue
Y
Rishikof
David C
DC
Jean
Jyh-Chang
JC
Joyce-Brady
Martin
M
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004549:Elastin / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D018496:Hyperoxia; D016023:Integrins / Q000502:physiology; D008024:Ligands; D008168:Lung / Q000187:drug effects; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010196:Pancreatic Elastase / Q000633:toxicity; D010446:Peptide Fragments / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; C492372:Fbln5 protein, rat; D016023:Integrins; D008024:Ligands; D010446:Peptide Fragments; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004549:Elastin; D010196:Pancreatic Elastase