Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction

Carnevali, S; Nakamura, Yoichi; Mio, Tadashi; Liu, X.; Takigawa, Keiichi; Romberger, Debra J.; Spurzem, John R.; Rennard, Stephen I.

doi:10.1152/ajplung.1998.274.4.l591

Cited by 70 publications

(78 citation statements)

References 27 publications

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“…Similarly, CSE causes suppression of proliferation (36), apoptosis (37), senescence (3), and inhibition of collagen gel contraction (38) in lung fibroblasts in vitro, and it reduces proliferation (39), chemotaxis, and collagen gel contraction (40) in lung fibroblasts from patients with COPD. Considering the structural support by lung fibroblasts, Akt may play an important role in maintenance of lung integrity by lung fibroblasts, because PI3K/Akt signaling is involved in the production of extracellular matrix proteins.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Induces Akt Protein Degradation by the Ubiquitin-Proteasome System

Kim

Lee

Huh

et al. 2011

Journal of Biological Chemistry

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Emphysema is one of the characteristic features of chronic obstructive pulmonary disease, which is caused mainly by cigarette smoking. Recent data have suggested that apoptosis and cell cycle arrest may contribute to the development of emphysema. In this study, we addressed the question of whether and how cigarette smoke affected Akt, which plays a critical role in cell survival and proliferation. In normal human lung fibroblasts, cigarette smoke extract (CSE) caused cell death, accompanying degradation of total and phosphorylated Akt (p-Akt), which was inhibited by MG132. CSE exposure resulted in preferential ubiquitination of the active Akt (myristoylated), rather than the inactive (T308A/S473A double mutant) Akt. Consistent with cytotoxicity, CSE induced a progressive decrease of phosphorylated human homolog of mouse double minute homolog 2 (p-HDM2) and phosphorylated apoptosis signal regulating kinase 1 (p-ASK1) with concomitant elevation of p53, p21, and phosphorylated p38 MAPK. Forced expression of the active Akt reduced both CSE-induced cytotoxicity and alteration in HDM2/p53/p21 and ASK1/p38 MAPK, compared with the inactive Akt. Of note, CSE induced expression of the tetratricopeptide repeat domain 3 (TTC3), known as a ubiquitin ligase for active Akt. TTC3 siRNAs suppressed not only CSE-induced Akt degradation but also CSE-induced cytotoxicity. Accordingly, rat lungs exposed to cigarette smoke for 3 months showed elevated TTC3 expression and reduced Akt and p-Akt. Taken together, these data suggest that cigarette smoke induces cytotoxicity, partly through Akt degradation via the ubiquitin-proteasome system, in which TTC3 acts as a ubiquitin ligase for active Akt.

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Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Induces Akt Protein Degradation by the Ubiquitin-Proteasome System

Kim

Lee

Huh

et al. 2011

Journal of Biological Chemistry

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“…Of these, nicotine, acrolein, and acetaldehyde seem to be key short-acting pharmacological agents (44). Interestingly, acrolein stimulates release of inflammatory cytokines and can alter cellular repair processes by impairing fibroblast function (45). Previous evidence of a role for ERK in matrix remodeling has also been shown using human fibroblasts, in which ERK was associated with inhibition of collagen type I expression (46).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke

Mercer

Kolesnikova

Sonett

et al. 2004

Journal of Biological Chemistry

158

172

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The interstitial collagenase matrix metalloproteinase-1 (MMP-1) is up-regulated in the lung during pulmonary emphysema. The mechanisms underlying this aberrant expression are poorly understood. Although cigarette smoking is the predominant cause of emphysema, only 15-20% of smokers develop the disease. To define the signaling pathways activated by smoke and to identify molecules responsible for emphysema-associated MMP-1 expression, we performed several in vitro and in vivo experiments. In this study, we showed that cigarette smoke directly induced MMP-1 mRNA and protein expression and increased the collagenolytic activity of human airway cells. Treatment with various chemical kinase inhibitors revealed that this response was dependent on the extracellular regulated kinase-1/2 (ERK) mitogen activated protein kinase pathway. Cigarette smoke increased phosphorylation of residues Thr-202 and Tyr-204 of ERK in airway lining cells and alveolar macrophages in mice at 10 days and 6 months of exposure. Moreover, analysis of lung tissues from emphysema patients revealed significantly increased ERK activity compared with lungs of control subjects. This ERK activity was evident in airway lining and alveolar cells. The identification of active ERK in the lungs of emphysema patients and the finding that induction of MMP-1 by cigarette smoke in pulmonary epithelial cells is ERKdependent reveal a molecular mechanism and potential therapeutic target for excessive matrix remodeling in smokers who develop emphysema.

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“…Cigarette smoke extract has been shown to hinder the viability of human lung fibroblast-derived cells by inducing apoptosis in lower concentrations (10-25%) and necrosis in higher concentrations (50-100%) [15]. Cigarette smoke extract is also known to inhibit lung fibroblast proliferation and chemotaxis [13] and to inhibit fibroblast-mediated collagen gel contraction [16].…”

Section: Discussionmentioning

confidence: 99%

Effects of tobacco smoking on findings in chest computed tomography among asbestos-exposed workers

Vehmas¹,

Kivisaari²,

Huuskonen³

et al. 2003

Eur Respir J

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Effects of tobacco smoking on findings in chest computed tomography among asbestosexposed workers. T. Vehmas, L. Kivisaari, M.S. Huuskonen, M.S. Jaakkola. #ERS Journals Ltd 2003. ABSTRACT: This study examined the effects of smoking on the findings in chest computed tomography (CT) in 587 asbestos-exposed construction workers (11 females, 576 males, mean age 62 yrs; 18 never-smokers, 406 exsmokers and 163 current smokers). The workers were imaged with spiral CT and high-resolution CT. A total of 13 radiological signs were scored by three radiologists independently. The workers9 medical data, smoking habits and occupational exposures were collected at an interview. The effects of smoking status and smoked pack-yrs (0-87.5) on the CT signs were studied using multivariate analysis adjusted for confounding factors.Smoking increased all emphysema signs and contributed to bronchial wall thickening. Smoking was negatively associated with curvilinear and septal lines as well as with parenchymal bands. In persons who had smoked v10 pack-yrs, smoking was positively related to paraseptal emphysema and to bronchial wall thickening and negatively related to septal lines, subpleural nodules and honeycombing.Smoking was related to several abnormal computed tomography signs even among those with relatively small exposure. Computed tomography can detect changes due to smoking at an early stage.

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Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction

Cited by 70 publications

References 27 publications

Cigarette Smoke Induces Akt Protein Degradation by the Ubiquitin-Proteasome System

Cigarette Smoke Induces Akt Protein Degradation by the Ubiquitin-Proteasome System

Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke

Effects of tobacco smoking on findings in chest computed tomography among asbestos-exposed workers

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