Sharing signals: connecting lung epithelial cells with gap junction channels

Koval, Michael

doi:10.1152/ajplung.00078.2002

Cited by 56 publications

(50 citation statements)

References 302 publications

(234 reference statements)

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“…In mouse lung, Cx32 is expressed in multipotent pulmonary alveolar type II cells (13). We evaluated the effect of Cx32-deficiency on lung tumorigenesis initiated with the carcinogen diethylnitrosamine, a tissue-specific carcinogen shown to cause tumors primarily in mouse liver and lung.…”

Section: Resultsmentioning

confidence: 99%

“…Cx32-Deficient Lung Tumors Express the Type II Alveolar Cell Marker Surfactant-associated Protein C. The adult mouse lung is predominantly composed of type I and type II pulmonary alveolar cells (13,19). Type I cells mediate gas exchange and occupy a majority of surface area in the adult mouse lung.…”

Section: Resultsmentioning

confidence: 99%

“…Cx32-deficient mice exhibit abnormal physiology as well as peripheral nerve demyelination reminiscent of human Charcot-Marie Tooth Syndrome (4). Although previous studies have established that connexins are expressed in the pulmonary system, the precise influence of connexins on development and physiology has yet to be determined (13)(14)(15)(16). Although several studies have suggested the influence of connexins on lung tumor cell behavior (12,17,18), no conclusive studies have linked connexin deficiency with pulmonary oncogenesis in situ.…”

Section: Introductionmentioning

confidence: 99%

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The Gap Junction Protein Connexin32 Is a Mouse Lung Tumor Suppressor

King

Lampe

2004

Cancer Research

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Although loss of connexin expression and/or gap junction intercellular communication correlates with decreased growth control and increased neoplastic potential, there is limited evidence directly linking gap junction intercellular communication function with tumor suppression in situ. Here, we show for the first time that a gap junction protein, connexin32 (Cx32), acts as a lung tumor suppressor in a mouse model. Cx32-deficient nontumorous lung tissue exhibited an increased proliferative index (P < 0.001), and, after exposure to the carcinogen diethylnitrosamine, Cx32-deficient mice exhibited a highly statistically significant (P < 0.001) increase in bronchioloalveolar lung tumor incidence (28 of 45, 62%) and a 45% increase in average multiplicity compared with wild-type mice (7 of 29, 24%). Tumors from Cx32-deficient mice also showed increased activation of mitogen-activated protein kinase (P < 0.001) compared with wild-type tumors, implicating this signaling pathway in Cx32/gap junction intercellular communication-associated lung tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Gap Junction Protein Connexin32 Is a Mouse Lung Tumor Suppressor

King

Lampe

2004

Cancer Research

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“…Alveolar epithelial cells show, however, great variability in the expression of connexins as a function of cell phenotype and cell state (Koval 2002). Under certain culture conditions, Cx43 was phenotype-specific for AT I cells (Isakson et al 2001).…”

Section: Discussionmentioning

confidence: 99%

A new rat type I-like alveolar epithelial cell line R3/1: bleomycin effects on caveolin expression

Koslowski¹,

Barth²,

Augstein³

et al. 2004

Histochem Cell Biol

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The study of function and regulation of the phenotype of alveolar type I (AT I) epithelial cells is limited by the rareness of suitable cell lines or primary cultures of this cell type. We describe in the present study the type I-like rat epithelial cell line R3/1. This cell line displays in vitro a phenotype with several characteristic features of AT I cells. R3/1 cells were analysed for mRNA and protein content of markers related to the AT I cell type (T1alpha, ICAM-1, connexin-43, caveolins-1 and -2) and AT II phenotypes [surfactant proteins (SPs) A, B, C and D]. The mRNAs for SPs were found to be at a low level. Moderate protein levels for SP-A and SP-B were found, and SP-C and SP-D proteins were not detectable. R3/1 cells are positive for CD44s, E-cadherin, cytokeratin, vimentin and RAGE, and bind the lectins BPA and SBA. For demonstration of the suitability of R3/1 cells for in vitro studies on epithelial injury, the cells were treated with bleomycin. As shown by real-time RT-PCR and immunoblotting, bleomycin-treatment of R3/1 cells resulted in a decrease in mRNA and protein for both caveolin-1 and caveolin-2 in comparison with controls. The AT I-like cell line R3/1 may serve as a promising tool for the study of lung cell biology.

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“…Communication between AEC I and AEC II can be accomplished by means of two major routes: gap junction and paracrine communication (Koval, 2002). What are the mechanisms for P2X 7 R-mediated AEC I and AEC II communication?…”

mentioning

confidence: 99%

Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner

Mishra

Chintagari

Guo

et al. 2011

Journal of Cell Science

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SummaryAlveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X 7 receptor (P2X 7 R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X 7 R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X 7 R) increased surfactant secretion, which was blocked by the P2X 7 R antagonist Brilliant Blue G. This effect was observed in AEC II cocultured with human embryonic kidney HEK-293 cells stably expressing rat P2X 7 R, but not when co-cultured with AEC I in which P2X 7 R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X 7 R -/-mice. BzATP-mediated secretion involved P2Y 2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y 2 receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X 7 R cells than with ATP alone. P2X 7 R -/-mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X 7 R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X 7 R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y 2 receptors in AEC II.

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Sharing signals: connecting lung epithelial cells with gap junction channels

Cited by 56 publications

References 302 publications

The Gap Junction Protein Connexin32 Is a Mouse Lung Tumor Suppressor

The Gap Junction Protein Connexin32 Is a Mouse Lung Tumor Suppressor

A new rat type I-like alveolar epithelial cell line R3/1: bleomycin effects on caveolin expression

Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner

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