Intestinal renin–angiotensin system is stimulated after deletion of Lkb1

Shorning, Boris; Jardé, Thierry; McCarthy, Afshan; Ashworth, Alan; Leng, Wendy W.J. de; Offerhaus, G. Johan A.; Resta, Nicoletta; Dale, Trevor; Clarke, Alan R.

doi:10.1136/gutjnl-2011-300046

Cited by 26 publications

(18 citation statements)

References 77 publications

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“…ACE and ACE2 are strongly expressed in the small intestine ( in fact, the highest human tissue concentrations of these enzymes are in intestine )47484950 and colon46, and neutral endopeptidase (neprilysin) shows similar patterns of expression51. AT 1 receptors are localized to the epithelial brush border, circular and longitudinal muscle layers and myenteric plexus of the small intestine, but AT 2 receptors are restricted to the myenteric plexus525354. AT 1 and AT 2 are also expressed in various layers of the colon46, stomach55, and esophagus5657.…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensinogen is expressed throughout the small intestine58, colon59, and stomach55. Various RAS peptides including angiotensin (Ang) I, Ang II, and Ang-(1-7) have been documented in various portions of the GI tract5260. Thus, the RAS is present in the viscera and it is therefore positioned to potentially play an important role in the control of digestive function.…”

Section: Discussionmentioning

confidence: 99%

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Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System

Weidemann

Voong

Morales-Santiago

et al. 2015

Sci Rep

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Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System

Weidemann

Voong

Morales-Santiago

et al. 2015

Sci Rep

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“…The latter include fluid shear stress, Ca 2+ -elevating agonists, and hormones, such as adiponectin. 29 At the outset of this study, circumstantial evidence suggested a link between fluid shear stress, the AMPK, and ACE expression as (1) ACE levels are decreased by shear stress, [8][9][10] (2) shear stress elicits activation of the AMPK, 14 (3) LKB1 (an AMPK kinase) was linked to ACE expression in the mouse intestine, 30 and (4) AMPK inhibition prevents the increase in ACE expression in macrophages induced by adipocyte-derived factors. 13 However, direct molecular links between the different events were missing.…”

Section: Discussionmentioning

confidence: 99%

AMP-Activated Protein Kinase Regulates Endothelial Cell Angiotensin-Converting Enzyme Expression via p53 and the Post-Transcriptional Regulation of microRNA-143/145

Kohlstedt

Trouvain

Boettger

et al. 2013

Circulation Research

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A ngiotensin II has been implicated in the pathobiology of atherosclerosis and in the arterial response to injury and restenosis via mechanisms that include vascular hypertrophy, extracellular matrix production, and cytokine induction. Although the angiotensin-converting enzyme (ACE) is only one of several enzymes that can generate angiotensin II, 1 the enzyme has been allocated a central role in cardiovascular disease development, mainly on the basis of the positive effects observed in response to ACE inhibitor therapy and experimental work involving protein downregulation.2 Certainly, ACE levels seem to correlate with disease development, and ACE protein has been detected in atherosclerotic human coronary 3,4 and carotid lesions. 5Relatively little is known about the signals that regulate ACE expression in vascular cells, but the exposure of vascular smooth muscle cells to fluid shear stress 6 or pulsatile pressure 7 is reported to increase expression of the enzyme. Although an identical phenomenon was initially reported in endothelial cells, 6 several other studies reported exactly the opposite, that is, that arterial levels of shear stress attenuate ACE promoter activity and decrease the expression of ACE mRNA in endothelial cells. [8][9][10] How can fluid shear stress regulate ACE expression? The first hypothesis was that the effects could be attributed to increased transcription as the genes for human, rat, and rabbit ACE all contain a number of shear stress-responsive elements in their promoter regions. These were however found to be inactive, and responsiveness to flow was then attributed to a combination of Barbie and GAGA response elements.

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“…69 (ii) Angiotensin receptors: AT1R has been localised to the epithelial brush border. 70 The circular and longitudinal muscle layers and the myenteric plexus also strongly express AT1R, but the AT2R appears to be largely restricted to the myenteric plexus. 71,72 Small vessels in the muscularis propria also express AT1R.…”

Section: Small Intestinementioning

confidence: 99%

“…76 (iv) Angiotensin peptides: Ang II has been detected in the crypt and crypt-villus junction epithelial cells. 70 To date, the expression of angiotensinogen, Ang I or Ang (1)(2)(3)(4)(5)(6)(7) in the human small intestine has not been reported. However, angiotensinogen has been widely localised in the rat brush border, epithelial cells, lamina propria, muscularis mucosa, submucosal blood vessels and muscularis propria.…”

Section: Small Intestinementioning

confidence: 99%

Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract

Garg

Angus

Burrell

et al. 2012

Aliment Pharmacol Ther

132

135

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Summary Background The renin‐angiotensin system (RAS) is a homeostatic pathway widely known to regulate cardiovascular and renal physiology; however, little is known about its influence in gastrointestinal tissues. Aim To elicit the anatomical distribution and physiological significance of the components of the RAS in the gastrointestinal tract. Methods An extensive online literature review including Pubmed and Medline. Results There is evidence for RAS involvement in gastrointestinal physiology and pathophysiology, with all the components required for autonomous regulation identified throughout the gastrointestinal tract. The RAS is implicated in the regulation of glucose, amino acid, fluid and electrolyte absorption and secretion, motility, inflammation, blood flow and possibly malignant disease within the gastrointestinal tract. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Given the ready availability of drugs that modify the RAS and their excellent safety profile, an opportunity exists for investigation of their possible therapeutic role in a variety of human gastrointestinal diseases. Conclusions The gastrointestinal renin‐angiotensin system appears to be intricately involved in a number of physiological processes, and provides a possible target for novel investigative and therapeutic approaches.

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Intestinal renin–angiotensin system is stimulated after deletion of Lkb1

Abstract: Taken together, these data reveal a novel role for Lkb1 in regulation of the gastrointestinal renin-angiotensin system.

Cited by 26 publications

References 77 publications

Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System

Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System

AMP-Activated Protein Kinase Regulates Endothelial Cell Angiotensin-Converting Enzyme Expression via p53 and the Post-Transcriptional Regulation of microRNA-143/145

Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract

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