Extracellular Matrix Fibronectin Increases Prostaglandin E2 Receptor Subtype EP4 in Lung Carcinoma Cells through Multiple Signaling Pathways

Han, ShouWei; Ritzenthaler, Jeffrey D.; Wingerd, Byron A.; Rivera, Hilda N.; Roman, Jesse

doi:10.1074/jbc.m610308200

Cited by 25 publications

(5 citation statements)

References 53 publications

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“…While it is well documented that extracellular matrices have significant effects on several cell types [56–59], the effect of extracellular matrices on cell metabolism have yet to be investigated. Because cell metabolism is altered in three-dimensional culture when compared to two-dimensional culture, this could have significant implications on the use of extracellular matrices because cell metabolism affects all of cellular physiology.…”

Section: Discussionmentioning

confidence: 99%

The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

Deorosan

Nauman

2011

Stem Cells International

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Mesenchymal stem cells (MSCs) have become a critical addition to all facets of tissue engineering. While most in vitro research has focused on their behavior in two-dimensional culture, relatively little is known about the cells' behavior in three-dimensional culture, especially with regard to their metabolic state. To evaluate MSC metabolism during twodimensional culture, murine bone marrow-derived MSCs were cultured for one week using twelve different medium compositions, varying in both glucose and fetal bovine serum (FBS) concentrations. The results indicate that glucose concentration was the more important factor in sustaining cell growth and viability. To evaluate metabolic state during three-dimensional culture, MSCs were cultured for one week using two different medium compositions and two different concentrations of collagen gel matrix. The medium compositions only varied in glucose concentration. The results indicate that glucose and extracellular matrix were significant factors in the metabolic response of the cells. However, cells cultured in low density collagen exhibited considerable cell death, likely because of physical contraction of the collagen hydrogel which was not observed in the higher density collagen. These findings will be useful to the development of in vitro cell culture models that properly mimic in vivo physiological processes.

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Section: Discussionmentioning

confidence: 99%

The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

Deorosan

Nauman

2011

Stem Cells International

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“…Notably, recent evidence suggests that nerve growth factor-induced human umbilical vein endothelial cell matrix metalloproteinase-2 production and Matrigel invasion are mediated via PI3K/Akt-dependent AP-2 activity (34). Similarly, extracellular matrix fibronectin, signaling via ␣5␤1 integrins, activates PI3K/Akt to enhance AP-2 binding to the EP4 promoter (35). Our data are compatible with these studies but suggest that the PI3K/Akt/PTEN axis more broadly regulates GPCR expression than was recognized previously.…”

Section: Discussionmentioning

confidence: 99%

Phosphatase and Tensin Homologue on Chromosome 10 (PTEN) Directs Prostaglandin E2-mediated Fibroblast Responses via Regulation of E Prostanoid 2 Receptor Expression

Sagana

Yan

Cornett

et al. 2009

Journal of Biological Chemistry

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Prostaglandin E 2 (PGE 2 ) is an arachidonic acid metabolite that counters transforming growth factor-␤-induced fibroblast activation via E prostanoid 2 (EP2) receptor binding. Phosphatase and tensin homologue on chromosome 10 (PTEN) is a lipid phosphatase that, by antagonizing the phosphoinositol 3-kinase (PI3K) pathway, also inhibits fibroblast activation. Here, we show that PTEN directly regulates PGE 2 inhibition of fibroblast activation by augmenting EP2 receptor expression. The increase in collagen production and ␣-smooth muscle actin expression observed in fibroblasts in which PTEN is deficient was resistant to the usual suppressive effects of PGE 2 . This was due to marked down-regulation of EP2, a G s protein-coupled receptor (GPCR) that mediates the inhibitory actions of this prostanoid via cAMP. pten ؊/؊ or PTEN-inhibited fibroblasts in which the PI3K pathway was blocked demonstrated a restoration of EP2 receptor expression, due to augmented gene transcription and mRNA instability. Importantly, restoration of the balance between PI3K and PTEN reestablished the inhibitory effect of PGE 2 on fibroblast activation. No such influence of PTEN was observed on alternative E prostanoid GPCRs. Moreover, our studies identified a positive feedback loop in which cAMP signaling enhanced EP2 receptor expression, independent of PTEN. Therefore, our findings indicate that PTEN regulates the antifibrotic effects of PGE 2 by a specific and permissive effect on EP2 receptor expression. Further, our data imply that cAMP signaling circumvents EP2 down-regulation in pten-deficient cells to restore EP2 receptor expression. This is the first description, to our knowledge, of PI3K/PTEN balance directing GPCR expression, and provides a novel mechanism for cellular effects of PTEN.Prostaglandin E 2 (PGE 2 ) 2 is a cyclooxygenase-derived metabolite of arachidonic acid that influences a spectrum of important biological processes including pain, inflammation, and fibrosis. PGE 2 effects may be cell-specific; for example, PGE 2 promotes migration of epithelial cells (1, 2), but it inhibits migration of fibroblasts (3, 4). These seemingly paradoxical actions of PGE 2 reflect the distinct responses resulting from ligation of a diverse repertoire of E prostanoid (EP) receptors on the cell surface. The four G protein-coupled (GPCR) EP receptors, termed EP1-4, signal by mobilizing intracellular calcium (EP1), increasing intracellular cAMP (EP2 and 4), or decreasing intracellular cAMP (EP3) (5). We have shown previously that PGE 2 is capable, in lung fibroblasts, of tempering the profibrotic, activating effects induced by TGF-␤ (e.g. ␣-smooth muscle actin (␣-SMA) and collagen I expression) (6) as well as the migratory effects of fibroblast growth factor (3). These effects are mediated by intracellular cAMP subsequent to binding of EP2, the most abundant of the fibroblast EP receptors.Phosphatase and tensin homologue on chromosome 10 (PTEN) is a dual specificity lipid and protein phosphatase, but its primary action involves dephosphorylat...

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“…Laminin from Engelbreth-Holm-Swarm murine sarcoma basement membrane (Sigma Chemicals, Inc., St. Louis, MO), rat tail type I collagen (Roche Diagnostics, Mannheim, Germany), and matrix fibronectin (Sigma Chemicals, Inc.) were dissolved in coating buffer (0.1 M NaHCO 3 [pH 8.5]) at a concentration of 20 mg/ml (36). Transwells (12-well; Corning Costar, Lowell, MA) received 1 ml per well and were incubated at 48C overnight.…”

Section: Coating Transwell Permeable Supports With Matrix Componentsmentioning

confidence: 99%

Extracellular Matrix Influences Alveolar Epithelial Claudin Expression and Barrier Function

Koval¹,

Ward²,

Findley³

et al. 2010

Am J Respir Cell Mol Biol

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The lung is dynamically remodeled in response to injury, which alters extracellular matrix composition, and can lead to either healthy or impaired lung regeneration. To determine how changes in extracellular matrix can influence alveolar epithelial barrier function, we examined the expression and function of tight junction proteins by rat alveolar epithelial type II cells cultured on one of three different matrix components: type I collagen or fibronectin, matrix glycoproteins which are highly expressed in injured lungs, or laminin, a basement membrane matrix component. Of note, alveolar epithelial cells cultured for 2 days on fibronectin formed high-resistance barriers and showed continuous claudin-3 and claudin-18 localization to the plasma membrane, as opposed to cells cultured on either type I collagen or laminin, which had low resistance monolayers and had areas of cell-cell contact that were claudin deficient. The barrier formed by cells cultured on fibronectin also had preferential permeability to chloride as compared with sodium. Regardless of the initial matrix composition, alveolar epithelial cells cultured for 5 days formed high-resistance barriers, which correlated with increased claudin-18 localization to the plasma membrane and an increase in zonula occludens-1. Day 5 cells on laminin had significantly higher resistance than cells on either fibronectin or type I collagen. Thus, although alveolar epithelial cells on fibronectin formed rapid barriers, it was at the expense of producing an optimized barrier.

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Extracellular Matrix Fibronectin Increases Prostaglandin E2 Receptor Subtype EP4 in Lung Carcinoma Cells through Multiple Signaling Pathways

Cited by 25 publications

References 53 publications

The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

Phosphatase and Tensin Homologue on Chromosome 10 (PTEN) Directs Prostaglandin E2-mediated Fibroblast Responses via Regulation of E Prostanoid 2 Receptor Expression

Extracellular Matrix Influences Alveolar Epithelial Claudin Expression and Barrier Function

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