Clara cell adhesion and migration to extracellular matrix

Atkinson, Jeffrey J.; Adair-Kirk, Tracy L.; Kelley, Diane G.; deMello, Daphne E.; Senior, Robert M.

doi:10.1186/1465-9921-9-1

Cited by 54 publications

(52 citation statements)

References 51 publications

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“…Finally, the lung epithelial cells were disseminated on culture dishes. Murine Clara cells were isolated and cultured as described (Atkinson et al, 2008). To stimulate cells with GST or GST fusion proteins, the cells were cultured with 50 ng/ml of GST, GST-S100A8 or GST-SAA3 in the presence of an endotoxin inhibitor polymixin B at 10 mg/ml for 6 h. GST, GST-S100A8 and GST-SAA3 recombinant proteins were overexpressed in Escherichia coli with pGEX-4T-2 vectors (GE Healthcare, Piscataway, NJ, USA) and purified by using glutathione Sepharose column (GE Healthcare).…”

Section: Clara Cell-ablationmentioning

confidence: 99%

Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis

et al. 2011

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We have previously shown that tumor necrosis factor (TNF)a produced from primary tumor-induced expression of two endogenous Toll-like receptor 4 (TLR4) ligands, S100A8 and serum amyloid A3 (SAA3), in pre-metastatic lungs. However, mechanistic details of the signaling network and relevance to pulmonary physiology are poorly understood. Here, we identify Clara cells as a control tower of the network. Clara cell ablation by naphthalene suppressed pulmonary recruitment of CD11b þ TLR4 þ cells and spontaneous lung metastasis. Clara cells turned out to express TLR4 through which SAA3 was auto-amplified. Reciprocal bone marrow transplantation between wild-type and TLR4 knockout mice demonstrated that pulmonary TLR4 þ Clara cells could be derived from bone marrow. SAA3-induced TNFa expression in both alveolar type II cells and macrophages. Primary co-cultures of alveolar type II cells and Clara cells revealed that the induction of TNFa in alveolar type II cells was dependent on the Clara cell-mediated amplification of SAA3. SAA3 induction by bacterial endotoxin also required both Clara cells and TLR4. Thus, pulmonary metastatic soil may feature deregulation of homeostatic inflammatory responses to constant assaults of microbes with endotoxin.

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Section: Clara Cell-ablationmentioning

confidence: 99%

Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis

et al. 2011

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“…The Clara cells were isolated from mouse lung as described previously (89). Briefly, the RV was cannulated and flushed with sterile PBS after anesthetizing the mice.…”

Section: Figurementioning

confidence: 99%

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice

Yao

Chung²,

Hwang³

et al. 2012

J. Clin. Invest.

315

351

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Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD + -dependent protein/histone deacetylase, is reduced in lungs of patients with COPD. However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown. Here, we showed increased cellular senescence in lungs of COPD patients. SIRT1 activation by both genetic overexpression and a selective pharmacological activator, SRT1720, attenuated stress-induced premature cellular senescence and protected against emphysema induced by cigarette smoke and elastase in mice. Ablation of Sirt1 in airway epithelium, but not in myeloid cells, aggravated airspace enlargement, impaired lung function, and reduced exercise tolerance. These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes. Inhibition of lung inflammation by an NF-κB/IKK2 inhibitor did not have any beneficial effect on emphysema. Thus, SIRT1 protects against emphysema through FOXO3-mediated reduction of cellular senescence, independently of inflammation. Activation of SIRT1 may be an attractive therapeutic strategy in COPD/emphysema.

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“…Expression of extracellular matrix (ECM) proteins in the provisional matrix are increased, and for Clara cells, factors like fibronectin and collagen I have been described to attract and provide adherence points for migration [8].…”

mentioning

confidence: 99%

Nerve growth factor enhances Clara cell proliferation after lung injury

Sonar¹,

Schwinge²,

Kılıç³

et al. 2010

Eur Respir J

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The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far.To investigate the repair function of NGF, experiments were performed in vitro using cultured alveolar epithelial cells and in vivo using a naphthalene-induced model of Clara epithelial cell injury.Both in vitro and in vivo experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented in vitro migration of alveolar type II cells. In vivo, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin in vitro and in vivo during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice.Our study demonstrates that NGF promotes the proliferation of lung epithelium in vitro and the renewal of Clara cells following lung injury in vivo.

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Clara cell adhesion and migration to extracellular matrix

Cited by 54 publications

References 51 publications

Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis

Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice

Nerve growth factor enhances Clara cell proliferation after lung injury

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