Cigarette smoke inhibits the growth of lung fibroblasts from patients with pulmonary emphysema

Nobukuni, Sumie; Watanabe, Kentaro; Inoue, Jun; Wen, Fuqiang; Tamaru, Noriko; Yoshida, Minoru

doi:10.1046/j.1440-1843.2002.00400.x

Cited by 31 publications

(30 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This was a surprising finding, since, at least in vitro, cigarette smoke extracts reduce viability and inhibit fibroblast proliferation and migration (16,27,29).…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs

Cisneros

Gaxiola²,

Ramos³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…This was a surprising finding, since, at least in vitro, cigarette smoke extracts reduce viability and inhibit fibroblast proliferation and migration (16,27,29).…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs

Cisneros

Gaxiola²,

Ramos³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…In addition to this, there is indication that lung repair, as evidenced by de novo synthesis and tissue accumulation of elastin and collagen, is inhibited by cigarette smoke [149]. Exposure to cigarette smoke extract also inhibits fibroblast proliferation [150], and fibroblasts isolated from patients with emphysema exhibit decreased proliferative capacity [151,152]. Exposure to cigarette smoke extract induces cell cycle arrest in fibroblasts, mediated through activation of p53 and p16, which inhibit the cell cycle, leading to cellular senescence [153], which may represent a response of fibroblasts to DNA damage by cigarette smoke extract [154].…”

Section: Emphysema and Fibrosismentioning

confidence: 99%

Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction

Chung¹,

Adcock²

2008

Eur Respir J

517

425

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease is a leading global cause of morbidity and mortality that is characterised by inexorable deterioration of small airways obstruction with emphysema associated with cellular inflammation and structural remodelling. Other features include apoptosis as well as proliferation of cells, and both tissue repair and lack of tissue repair.Metalloprotease release, together with that of apoptotic factors, may underlie the emphysema, and, conversely, fibrosis of the small airways may be accounted for by the effects of growth factor activation. In advanced disease, influential factors include the development of autoimmunity, with activation of dendritic cells and T-helper cells of both type 1 and 2, and the senescence response.An inability of macrophages to ingest apoptosed cells and bacteria may exacerbate inflammatory responses. Systemic inflammation with concomitant cardiovascular disease and metabolic syndrome may reflect the effect of cigarette smoke on nonpulmonary cells. Corticosteroid resistance may be secondary to oxidative stress mechanisms, such as inactivation of histone deacetylases.The mechanisms of chronic obstructive pulmonary disease may be heterogeneous, according to severity, and clinical phenotypes need to be correlated with cellular and pathological processes. Treatments may be targeted to patients with specific mechanisms.

show abstract

“…Lung fibroblasts isolated from patients with emphysema show a decreased proliferative capacity, suggesting cellular senescence due to exposure to cigarette smoke (10,11,35). Senescent cells have a markedly reduced proliferative capacity, but still maintain their viability with an increase in senescence associated ␤-galactosidase (SA ␤-gal) activity (21).…”

Section: A Short-term Exposure To Cse Induces Growth Inhibition But mentioning

confidence: 99%

Cigarette Smoke Induces Cellular Senescence

Nyunoya¹,

Monick²,

Klingelhutz³

et al. 2006

Am J Respir Cell Mol Biol

242

223

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and cigarette smoking is the major risk factor for COPD. Fibroblasts play an important role in repair and lung homeostasis. Recent studies have demonstrated a reduced growth rate for lung fibroblasts in patients with COPD. In this study we examined the effect of cigarette smoke extract (CSE) on fibroblast proliferative capacity. We found that cigarette smoke stopped proliferation of lung fibroblasts and upregulated two pathways linked to cell senescence (a biological process associated with cell longevity and an inability to replicate), p53 and p16-retinoblastoma protein pathways. We compared a single exposure of CSE to multiple exposures over an extended time course. A single exposure to CSE led to cell growth inhibition at multiple phases of the cell cycle without killing the cells. The decrease in proliferation was accompanied by increased ATM, p53, and p21 activity. However, several important senescent markers were not present in the cells at an earlier time point. When we examined multiple exposures to CSE, we found that the cells had profound growth arrest, a flat and enlarged morphology, upregulated p16, and senescenceassociated ␤-galactosidase activity, which is consistent with a classic senescent phenotype. These observations suggest that while a single exposure to cigarette smoke inhibits normal fibroblast proliferation (required for lung repair), multiple exposures to cigarette smoke move cells into an irreversible state of senescence. This inability to repair lung injury may be an essential feature of emphysema.

show abstract

Cigarette smoke inhibits the growth of lung fibroblasts from patients with pulmonary emphysema

Cited by 31 publications

References 12 publications

Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs

Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs

Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction

Cigarette Smoke Induces Cellular Senescence

Contact Info

Product

Resources

About