Gastrointestinal lymphatics in health and disease

Alexander, Jonathan; Ganta, Vijay Chaitanya; Jordan, Paul; Witte, Marlys H.

doi:10.1016/j.pathophys.2009.09.003

Cited by 101 publications

(92 citation statements)

References 212 publications

(221 reference statements)

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“…This is not the case in Pecam1 nulls. Although Sdc4 −/− and some Sdc4 −/− ; Pecam1 −/− double-knockout mice can survive to adulthood, the presence of abnormal lymphatic valves in the adult may affect the function of lymphatic vessels leading to increased morbidity (Alexander et al, 2010). The more severe lymphatic phenotype that developed in Sdc4 −/− ; Pecam1 −/− double nulls suggests that Sdc4 and Pecam1 function through independent flow signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Wang¹,

Baeyens²,

Corti³

et al. 2016

Journal of Cell Science

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The role of fluid shear stress in vasculature development and remodeling is well appreciated. However, the mechanisms regulating these effects remain elusive. We show that abnormal flow sensing in lymphatic endothelial cells (LECs) caused by Sdc4 or Pecam1 deletion in mice results in impaired lymphatic vessel remodeling, including abnormal valve morphogenesis. Ablation of either gene leads to the formation of irregular, enlarged and excessively branched lymphatic vessels. In both cases, lymphatic valve-forming endothelial cells are randomly oriented, resulting in the formation of abnormal valves. These abnormalities are much more pronounced in Sdc4 −/− ; Pecam1 −/− double-knockout mice, which develop severe edema. In vitro, SDC4 knockdown human LECs fail to align under flow and exhibit high expression of the planar cell polarity protein VANGL2. Reducing VANGL2 levels in SDC4 knockdown LECs restores their alignment under flow, while VANGL2 overexpression in wild-type LECs mimics the flow alignment abnormalities seen in SDC4 knockdown LECs. SDC4 thus controls flow-induced LEC polarization via regulation of VANGL2 expression.

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Section: Discussionmentioning

confidence: 99%

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Wang¹,

Baeyens²,

Corti³

et al. 2016

Journal of Cell Science

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“…For example, multiple organ dysfunction syndrome, "MODS," secondary to hemorrhagic shock and intestinal ischemia, is mediated by cytokines and lipid mediators produced in the gut and carried in lymph, but not portal venous plasma. 26,27) On the other hand, inflammatory cytokines produced in visceral fat deposited around the mesentery and omental are considered causative of systemic insulin resistance observed in obese patients with metabolic syndrome. [28][29][30] If these cytokines are carried in lymph to the circulation, MLNs likely play an important role in the pathophysiology of metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Identification of Acyl-CoA Thioesterase in Mouse Mesenteric Lymph Nodes

Ohtomo

Nakao

Sumiya

et al. 2013

Biological & Pharmaceutical Bulletin

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Acyl-CoA thioesterases (ACOTs) are a group of enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and CoA, with the potential to regulate the intracellular levels of these molecules. In this study, we show that a cytosolic isoform, ACOT7, is expressed at a significant level in the mesenteric lymph nodes (MLNs) of mice. While crude preparations of the mesenteric visceral fat contained significant levels of palmitoyl-CoA thioesterase activity, enzyme activity was concentrated 6.9-fold in MLNs compared with the residual adipose portion after excision of MLNs. When MLN homogenates were centrifuged, 82% of the enzyme activity was recovered in the cytosolic fraction, concomitant with almost exclusive recovery of ACOT7. Immunoprecipitation using anti-ACOT7 antibody estimated that 87% of enzyme activity in the homogenates was accounted for by ACOT7. On MLN sections, the germinal centers of secondary lymphoid follicles were immunostained with the antibody. In MLNs of mice fasted for 16 h, ACOT7 levels were induced 1.8-fold, which reflected a 1.5-fold increase in enzyme activity. These findings suggest that ACOT7 may be involved in dietary intake-associated responses in fatty acid metabolism in MLNs.Key words acyl-CoA thioesterase; acyl-CoA thioesterase 7; mesenteric lymph node; visceral fat Acyl-CoA thioesterases (ACOTs) comprise a group of enzymes that catalyze the hydrolysis of fatty acyl-CoA thioesters to corresponding free fatty acids and CoA. To date, 15 mammalian genes have been identified as ACOT family members.1-4) While ACOTs have the potential to regulate the intracellular levels of acyl-CoAs, free fatty acids, and CoA, their physiological functions are not fully understood. However, recent gene-knockout studies on a subgroup of ACOTs revealed that they profoundly affect lipid homeostasis in association with fatty liver development, obesity, and insulin resistance.5-7) Of the ACOT family members, ACOT1 (cytosolic), ACOT2 (mitochondrial), and ACOT7 (cytosolic) have been well characterized for their enzymatic properties (see refs. 1 and 3 for a review). These ACOTs share a common feature in that their expression is markedly induced by ligands for peroxisome proliferator-activated receptor α (PPARα), a nuclear receptor that regulates lipid metabolism-related genes, including the fibrate-class of hypolipidemic drugs. Moreover, ACOT1 and ACOT2 have been implicated in fatty acid catabolism, as emphasized by their upregulation in the liver and heart of fasted or high-fat diet-fed animals. [8][9][10][11] However, ACOT7 has enzyme activity two orders of magnitude higher than ACOT1 and ACOT2, and its expression is prominent in neurons of the central and peripheral nervous systems. [12][13][14] Thus, ACOT7 may have a role in cellular events other than energy metabolism, as the overexpression of ACOT7 in a macrophage cell line modified the production of prostaglandins.15) Recently, we examined the expression of ACOTs in fat tissues of rats 16,17) and unexpectedly found a significant level of acyl-Co...

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“…This circulatory switch increases mesenteric lymph flow and favors gut-derived factors that could reach the systemic circulation avoiding the liver filter [22,23].…”

Section: The Ischemia-reperfusion Phenotype: the Hydroelectrolitic Chmentioning

confidence: 99%

“…Expansion of lymphatics is also a prominent feature of gastrointestinal inflammation. The dysregulation of lymphatics exacerbates, in turn, gastrointestinal disease [83]. During cirrhotic portal hypertension dilation of esophageal and gastric lymph vessels may be related to the absorption of excess interstitial fluid [84].…”

Section: Ascites: the Portal Hypertensive Peritoneummentioning

confidence: 99%

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

Aller¹,

Arias²,

Prieto³

et al. 2012

ABB

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Prehepatic portal hypertension induces a splanchnic low-grade inflammatory response that could switch to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease. The extraembryonic origin of the portal system maybe determines the regression to an extraembryonic phenotype, i.e., vitellogenic and amniotic, during the evolution of both types of portal hypertension. Thus, prehepatic portal hypertension, or compensated hypertension by portal vein ligation in the rat, is associated with molecular mechanisms related to vitellogenesis, where hepatic steatosis and splanchnic angiogenesis stand out. In turn, extrahepatic cholestasis in the rat induces intrahepatic portal hypertension, or decompensated hypertension, with ascites and hepatorenal syndrome. The splanchnic interstitium, the mesenteric lymphatic system, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of ascites. The hypothetical comparison between the ascitic and the amniotic fluid also allows for translational investtigation. The induced regression of the splanchnic system to extraembryonic functions by portal hypertension highlights the great relevance of the extraembryonic structures even during post-natal life.

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Gastrointestinal lymphatics in health and disease

Cited by 101 publications

References 212 publications

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Identification of Acyl-CoA Thioesterase in Mouse Mesenteric Lymph Nodes

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

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