Fibroproliferation in LPS-induced airway remodeling and bleomycin-induced fibrosis share common patterns of gene expression.
Chronic LPS inhalation causes submucosal thickening and airway narrowing. To address the hypothesis that environmental airway disease is, in part, a fibroproliferative lung disease, we exposed C57BL/6 mice daily to LPS by inhalation for up to 2 months followed by 1 month of recovery. C57BL/6 mice exposed to daily inhaled LPS had significantly enhanced mRNA expression of TGF-beta1, TIMP-1, fibronectin-1, and pro-collagen types I, III, and IV and show prominent submucosal expression of the myofibroblast markers desmin and alpha-smooth muscle actin. To further characterize global gene expression in airway fibroproliferation, we performed microarray analysis on total lung RNA from mice exposed to LPS both acutely and chronically. This analysis revealed a subset of genes typically associated with lung injury and repair, and ECM homeostasis. To further identify candidate genes specifically involved in generic fibroproliferation, we interrogated this analysis with genes induced in C57BL/6 mouse lung by bleomycin. This analysis yielded a list of 212 genes in common suggesting that there is a common subset of genes that regulate fibroproliferation in the lung independent of etiologic agent and site of injury.
Department of Pediatrics/Neonatology, Duke University Medical Center, 403 Alex R. Sands Laboratory Building, DUMC 3373, Durham, NC 27710, USA. david.brass@duke.edu
David M
DM
Brass
Ivana V
IV
Yang
Marcus P
MP
Kennedy
Gregory S
GS
Whitehead
Holly
H
Rutledge
Lauranell H
LH
Burch
David A
DA
Schwartz
D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012137:Respiratory System
D015415:Biomarkers; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D001761:Bleomycin