title: Expression of profibrotic mediators in small airways versus parenchyma after cigarette smoke exposure.
abstract: Cigarette smoke-induced lung disease presents a morphologic contradiction in that the small airways become fibrotic but the parenchyma becomes emphysematous over time. To examine the mechanisms behind these phenomena, we exposed mice to cigarette smoke for up to 6 months and isolated small airways from histologic sections by laser capture microdissection. We then removed residual airway tissue and vessels, and collected the remaining parenchymal tissue. Gene expression of 13 fibrogenic growth/signaling factors (particularly TGF-beta-related genes), matrix proteins, or enzymes involved in matrix production was examined by real-time RT-PCR. Combining present and previously published data from our laboratory, in the airways over the long term there was a sustained and marked increase in expression of almost all of these genes. By contrast, in the parenchyma, expression of most genes was elevated at 2 and 24 hours after initial exposure, and all were elevated at 1 month; but by 6 months, when emphysema was present, most genes (9/13) were either at control values or down-regulated below control. At 3 months, several genes that were considerably elevated at 1 month were back to control levels, suggesting that loss of the parenchymal response precedes the development of emphysema. We conclude that with smoke exposure the airways demonstrate an ongoing profibrotic/proelastogenic response and the parenchyma a generally anti-fibrotic/anti-elastogenic response, but one that develops only with long-term exposure to smoke. These observations support the idea that the parenchyma largely fails to repair smoke-induced matrix damage, but this phenomenon is a relatively late event.
authors: Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 Canada. achurg@interchange.ubc.ca
authors: Andrew
authors: A
authors: Churg
authors: Steven
authors: S
authors: Zhou
authors: Olena
authors: O
authors: Preobrazhenska
authors: Hsin
authors: H
authors: Tai
authors: Rona
authors: R
authors: Wang
authors: Joanne L
authors: JL
authors: Wright
mesh_terms: D000818:Animals; D055745:Bronchioles / Q000473:pathology / Q000502:physiology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004646:Emphysema / Q000473:pathology / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007834:Lasers; D008168:Lung / Q000033:anatomy & histology* / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D042282:Microdissection; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D012906:Smoke; D053773:Transforming Growth Factor beta1; D003094:Collagen