NF-κB activates fibronectin gene expression in rat hepatocytes

Lee, Byung Heon; Park, Seung Yoon; Kang, Kae Bok; Park, Rang Woon; Kim, In San

doi:10.1016/s0006-291x(02)02356-2

Cited by 41 publications

(30 citation statements)

References 23 publications

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“…Fibronectin expression is regulated by p65/p65 homodimers [Lee et al, 2002]. In our study, fibronectin is significantly enhanced by microgravity, while an additional bFGF treatment does not have any effect on the level of fibronectin.…”

Section: Discussionsupporting

confidence: 38%

Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity

Ulbrich

Westphal

Baatout

et al. 2008

J of Cellular Biochemistry

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Fibroblast growth factors interact with appropriate endothelial cell (EC) surface receptors and initiate intracellular signal cascades, which participate in modulating blood vessel growth. EC, upon exposure to basic fibroblast growth factors (bFGFs) undergo profound functional alterations, which depend on their actual sensitivity and involve gene expression and de novo protein synthesis. We investigated the effects of bFGF on signaling pathways of EA.hy926 cells in different environments. EC were cultured under normal gravity (1 g) and simulated microgravity (micro g) using a three-dimensional (3D) clinostat. Microgravity induced early and late apoptosis, extracellular matrix proteins, endothelin-1 (ET-1) and TGF-beta(1) expression. Microgravity reduced eNOS mRNA within 24 h. Moreover, a six- to eightfold higher amount of IL-6 and IL-8 was secreted within 24 h micro g. In addition, microgravity induced a duplication of NF-kappaB p50, while p65 was quadrupled. At 1 g, bFGF application (4 h) reduced ET-1, TGF-beta(1) and eNOS gene expression. After 24 h, bFGF enhanced fibronectin, VEGF, Flk-1, Flt-1, the release of IL-6, IL-8, and TGF-beta(1). Furthermore, bFGF promoted apoptosis, reduced NFkB p50, but enhanced NFkB p65. After 4 h micro g, bFGF decreased TGF-beta(1), eNOS, and ET-1 gene expression. After 24 h micro g, bFGF elevated fibronectin, Flk-1 and Flt-1 protein, and reduced IL-6 and IL-8 compared with vehicle treated micro g cultures. In micro g, bFGF enhanced NF-KappaB p50 by 50%, Bax by 25% and attenuated p65, activation of caspase-3 and annexin V-positive cells. bFGF differently changes intracellular signals in ECs depending whether it is applied under microgravity or normal gravity conditions. In microgravity, bFGF contributes to protect the EC from apoptosis.

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Section: Discussionsupporting

confidence: 38%

Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity

Ulbrich

Westphal

Baatout

et al. 2008

J of Cellular Biochemistry

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“…5C). FN1 is a known NF-kB target gene (26). Our results showed that ILKAkt-NF-kB signaling is required for a-catulin-promoted cancer invasiveness.…”

Section: Aacrjournalsorg Downloaded Frommentioning

confidence: 59%

α-Catulin Drives Metastasis by Activating ILK and Driving an αvβ3 Integrin Signaling Axis

et al. 2013

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a-Catulin is an oncoprotein that helps sustain proliferation by preventing cellular senescence. Here, we report that a-catulin also drives malignant invasion and metastasis. a-Catulin was upregulated in highly invasive nonsmall cell lung cancer (NSCLC) cell lines, where its ectopic expression or short-hairpin RNA-mediated attenuation enhanced or limited invasion or metastasis, respectively. a-Catulin interacted with integrin-linked kinase (ILK), a serine/threonine protein kinase implicated in cancer cell proliferation, antiapoptosis, invasion, and angiogenesis. Attenuation of ILK or a-catulin reciprocally blocked cell migration and invasion induced by the other protein. Mechanistic investigations revealed that a-catulin activated Akt-NF-kB signaling downstream of ILK, which in turn led to increased expression of fibronectin and integrin avb3. Pharmacologic or antibodymediated blockade of NF-kB or avb3 was sufficient to inhibit a-catulin-induced cell migration and invasion. Clinically, high levels of expression of a-catulin and ILK were associated with poor overall survival in patients with NSCLC. Taken together, our study shows that a-catulin plays a critical role in cancer metastasis by activating the ILK-mediated Akt-NF-kB-avb3 signaling axis. Cancer Res; 73(1); 428-38. Ó2012 AACR.

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“…Thus, both ob/ob-and db/db-derived HSCs exposed to endotoxin developed an inflammatory and fibrogenic phenotype, whereas this response was observed in the livers of db/db mice but not in ob/ob mice following CCl 4 treatment, supporting a role for leptin as a proinflammatory factor required to amplify inflammatory reactions in vivo (28). Thus, proinflammatory cytokines increase fibronectin mRNA levels and protein deposition through a NF-B-dependent pathway in HSCs isolated from leptin-deficient mice (29). Indeed, in a variety of murine knockout models lacking a proinflammatory factor, such as cytokines, the overall inflammation in vivo is strongly reduced, whereas immune cells are still able to respond to inflammatory stimuli in vitro (35,58).…”

Section: Discussionmentioning

confidence: 90%

Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis

Brun

Castagliuolo

Leo³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

735

616

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October 5, 2006; doi:10.1152/ajpgi.00024.2006.-A small percentage of pathologically obese subjects with fatty livers develop histological signs of necroinflammation and fibrosis, suggesting a variety of cofactors in the pathogenesis of obesity-related liver diseases including nonalcoholic steatohepatitis. Since several observations have linked bacterial endotoxins to liver damage, the aim of this study was to determine the effect of obesity on intestinal mucosal integrity and portal blood endotoxemia in two strains of obese mice: leptin-deficient (ob/ob) and hyperleptinemic (db/db) mice. Murine intestinal mucosal barrier function was assessed using a Ussing chamber, whereas ileum tight junction proteins were analyzed by immunocytochemistry and Western blot analysis. Circulating proinflammatory cytokines and portal blood endotoxin levels were measured by ELISA and the limulus test, respectively. The inflammatory and fibrogenic phenotype of murine hepatic stellate cells (HSCs) was determined by ELISA and quantitative RT-PCR. Ob/ob and db/db mice showed lower intestinal resistance, profoundly modified distribution of occludin and zonula occludens-1 in the intestinal mucosa, and higher circulating levels of inflammatory cytokines and portal endotoxemia compared with lean control mice. Moreover, HSCs isolated from ob/ob and db/db mice showed higher membrane CD14 mRNA levels and more pronounced lipopolysaccharide-induced proinflammatory and fibrogenic responses than HSCs from lean animals. In conclusion, genetically obese mice display enhanced intestinal permeability leading to increased portal endotoxemia that makes HSCs more sensitive to bacterial endotoxins. We suggest that in metabolic syndrome, patients may likewise have a greater intestinal mucosa permeability and increased lipopolysaccharide levels in portal blood that can contribute to the liver inflammatory damage.

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NF-κB activates fibronectin gene expression in rat hepatocytes

Cited by 41 publications

References 23 publications

Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity

Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity

α-Catulin Drives Metastasis by Activating ILK and Driving an αvβ3 Integrin Signaling Axis

Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis

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