title: Regional heterogeneity in murine lung fibroblasts from normal mice or mice exposed once to cigarette smoke.
abstract: Chronic obstructive lung disease (COPD) is characterized by matrix deposition in the small airways but matrix loss from the parenchyma, phenomena which must depend on the ability of local fibroblasts to produce matrix after smoke exposure. To investigate this idea, we exposed C57Bl/6 mice once to cigarette smoke or to air (control) and prepared primary cultures of lung fibroblasts by microdissecting large airways (trachea, LAF), medium size airways (major bronchi, MAF) and parenchyma (PF). Control PF showed the lowest rate of wound closure and wound closure was depressed in all lines by a single in vivo smoke exposure. Gene expression of matrix proteins differed considerably among the sites; decorin, which may sequester TGFβ, was markedly higher in PF. PF showed higher intrinsic ratios of pSmad2/Smad2. Smoke caused much greater increases in secreted and matrix deposited collagens 1 and 3 in PF than in LAF or MAF. Expression of Thy-1, a gene that suppresses myofibroblast differentiation, was increased by smoke in PF. We conclude that there is considerable regional heterogeneity in murine lung fibroblasts in terms of matrix production, either basally or after in vivo smoke exposure; that PF have lower ability to repair wounds and higher intrinsic TGFβ signaling; and that a single exposure to smoke produces lasting changes in the pattern of matrix production and wound repair, changes that may be mediated in part by smoke-induced release of TGFβ. However, PF still retain the ability to repair by producing new matrix after a single in vivo smoke exposure.
authors: Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Olena
authors: O
authors: Preobrazhenska
authors: Joanne L
authors: JL
authors: Wright
authors: Andrew
authors: A
authors: Churg
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D015398:Signal Transduction; D012906:Smoke; D014026:Nicotiana; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
chemical_list: D016326:Extracellular Matrix Proteins; D012906:Smoke; D016212:Transforming Growth Factor beta