Increased expression of the urokinase plasminogen activator system by <i>Helicobacter pylori</i> in gastric epithelial cells

Kenny, Susan; Duval, Cédric; Sammut, Stephen‐John; Steele, Islay; Pritchard, D. Mark; Atherton, John C.; Argent, Richard H.; Dimaline, R.; Dockray, Graham J.; Varró, Andrea

doi:10.1152/ajpgi.90283.2008

Cited by 28 publications

(47 citation statements)

References 59 publications

(82 reference statements)

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“…In addition to the physiological mechanisms by which gut signals influence food intake, it is also clear that interactions between the gut microbiota and immune and nervous systems can profoundly influence energy balance. We now report that PAI-1, which is increased in plasma in obesity (5, 6), and in stomach with Helicobacter infection (3, 4), acts as a gastric factor suppressing satiety signals. Specifically, the data suggest that PAI-1 suppresses gut-brain signaling by CCK, thereby increasing food intake.…”

Section: Discussionmentioning

confidence: 76%

“…Because Helicobacter infection increases gastric PAI-1 (3), we then examined food intake in H. felis -infected C57BL/6, PAI-1-H/Kβ, and PAI-1 −/− mice. Confirming previous findings, PAI-1 mRNA was approximately 2-fold higher in the gastric corpus of infected compared with control mice (100 ± 3 vs 206 ± 18, P < .05).…”

Section: Resultsmentioning

confidence: 99%

“…Gut-derived signals that inhibit energy intake include brain-gut peptides, eg, cholecystokinin (CCK); proinflammatory cytokines, eg, IL1β; and adipokines, eg, leptin (2). Recent work suggests that the adipokine plasminogen activator inhibitor (PAI)-1, which is elevated in plasma in obesity, is also produced in gut epithelial and subepithelial cells, raising the possibility of novel roles in gastrointestinal (GI) function and energy balance (3, 4). …”

mentioning

confidence: 99%

“…Because PAI-1 inhibits thrombolysis by inhibition of uPA and tPA and is elevated in obesity, it has been suggested to play a role in the increased risk of vascular occlusive disease in obesity (5, 6). In the stomach, PAI-1 is expressed in parietal and enterochromaffin-like cells, and expression is increased in Helicobacter pylori infection (3) and with elevated plasma gastrin concentrations (7). However, the role of PAI-1 in gastric function and a possible link to metabolic function is virtually unexplored.…”

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confidence: 99%

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Gastric Expression of Plasminogen Activator Inhibitor (PAI)-1 Is Associated with Hyperphagia and Obesity in Mice

et al. 2013

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The adipokine plasminogen activator inhibitor (PAI)-1 is increased in plasma of obese individuals and exhibits increased expression in the stomachs of individuals infected with Helicobacter. To investigate the relevance of gastric PAI-1, we used 1.1 kb of the H+/K+β subunit promoter to overexpress PAI-1 specifically in mouse gastric parietal cells (PAI-1-H/Kβ mice). We studied the physiological, biochemical, and behavioral characteristics of these and mice null for PAI-1 or a putative receptor, urokinase plasminogen activator receptor (uPAR). PAI-1-H/Kβ mice had increased plasma concentrations of PAI-1 and increased body mass, adiposity, and hyperphagia compared with wild-type mice. In the latter, food intake was inhibited by cholecystokinin (CCK)8s, but PAI-1-H/Kβ mice were insensitive to the satiating effects of CCK8s. PAI-1-H/Kβ mice also had significantly reduced expression of c-fos in the nucleus tractus solitarius in response to CCK8s and refeeding compared with wild-type mice. Exogenous PAI-1 reversed the effects of CCK8s on food intake and c-fos levels in the nucleus tractus solitarius of wild-type mice, but not uPAR-null mice. Infection of C57BL/6 mice with Helicobacter felis increased gastric abundance of PAI-1 and reduced the satiating effects of CCK8s, whereas the response to CCK8s was maintained in infected PAI-1–null mice. In cultured vagal afferent neurons, PAI-1 inhibited stimulation of neuropeptide Y type 2 receptor (Y2R) expression by CCK8s. Thus, gastric expression of PAI-1 is associated with hyperphagia, moderate obesity, and resistance to the satiating effects of CCK indicating a new role in suppressing signals from the upper gut that inhibit food intake.

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Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Gastric Expression of Plasminogen Activator Inhibitor (PAI)-1 Is Associated with Hyperphagia and Obesity in Mice

et al. 2013

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“…Several in vitro studies have found that the expression of uPAR is upregulated in cancer and gastric epithelial cell lines when co-cultured with H. pylori (Guillemin, Salama, Tompkins, & Falkow, 2002;Sepulveda et al, 2002;El-Etr, Mueller, Tompkins, Falkow, & Merrell, 2004;Iwamoto et al, 2005;Kim et al, 2005;Kim et al, 2007;Iwamoto, Mizokami, Takahashi, Matsuoka, & Matsuzaki, 2008). This phenomenon has also been documented in vivo, specifically in non-neoplastic tissue (adjacent to the tumor growth) obtained from GC patients (Alpízar-Alpízar et al, 2010), as well as in gastric biopsies from patients that have no cancer but are infected with the bacterium (Kenny et al, 2008). In addition, one study reported a significant correlation between uPAR expression in neoplastic tissue and presence of H. pylori in adjacent non-neoplastic tissue (Beyer et al, 2006).…”

Section: Plasminogen Activation System and Helicobacter Pylorimentioning

confidence: 82%

La importancia del sistema activador de plasminógeno en la patogénesis y progresión del cáncer gástrico

Alpízar‐Alpízar

Malespín-Bendaña

Une

et al. 2017

RBT

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Gastric cancer is ranked as the third death-causing cancer and one of the most incident malignancies worldwide. Although Helicobacter pylori is the most well-established risk factor for the development of this neoplasm, most of the infected individuals do not develop gastric cancer. Two of the main challenges faced by the world's scientific community in the combat against gastric cancer are the unraveling of its pathogenesis and the identification of novel ways to bring down the mortality. Malignant cell invasion of the non-neoplastic adjacent tissue and metastasis are pivotal events during cancer development and progression. Both processes are facilitated by proteases capable of degrading components of the extracellular matrix, some of which have been associated to clinic-pathological aspects of the disease. Recent studies have suggested the possible connection between H. pylori and the expression of some of these proteases in gastric mucosa. This review summarizes the current knowledge about epidemiological, clinical and biological aspects of gastric cancer; it also discusses the main findings about the involvement of the plasminogen activation system in the development and progression of this disease, as well as its potential repercussions in the clinical setting. Rev. Biol. Trop. 66(1): 28-47. Epub 2018 March 01.

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Magnetically enhanced nucleic acid delivery. Ten years of magnetofection—Progress and prospects

Plank

Zelphati

Mykhaylyk

2011

Advanced Drug Delivery Reviews

295

230

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Nucleic acids carry the building plans of living systems. As such, they can be exploited to make cells produce a desired protein, or to shut down the expression of endogenous genes or even to repair defective genes. Hence, nucleic acids are unique substances for research and therapy. To exploit their potential, they need to be delivered into cells which can be a challenging task in many respects. During the last decade, nanomagnetic methods for delivering and targeting nucleic acids have been developed, methods which are often referred to as magnetofection. In this review we summarize the progress and achievements in this field of research. We discuss magnetic formulations of vectors for nucleic acid delivery and their characterization, mechanisms of magnetofection, and the application of magnetofection in viral and nonviral nucleic acid delivery in cell culture and in animal models. We summarize results that have been obtained with using magnetofection in basic research and in preclinical animal models. Finally, we describe some of our recent work and end with some conclusions and perspectives.

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Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells

Abstract: Kenny S, Duval C, Sammut SJ, Steele I, Pritchard DM, Atherton JC, Argent RH, Dimaline R, Dockray GJ, Varro A. Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells.

Cited by 28 publications

References 59 publications

Gastric Expression of Plasminogen Activator Inhibitor (PAI)-1 Is Associated with Hyperphagia and Obesity in Mice

Gastric Expression of Plasminogen Activator Inhibitor (PAI)-1 Is Associated with Hyperphagia and Obesity in Mice

La importancia del sistema activador de plasminógeno en la patogénesis y progresión del cáncer gástrico

Magnetically enhanced nucleic acid delivery. Ten years of magnetofection—Progress and prospects

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