CYTOSKELETAL DISARRANGEMENT IN RAT INTESTINAL EPITHELIUM AFTER <i>IN VIVO</i> EXPOSURE TO SECRETAGOGUES

Hansson, Hans‐Arne; Lange, Stefan; Lönnroth, Ivar; Rozell, Björn; Tinberg, Harold M.

doi:10.1111/j.1699-0463.1984.tb02801.x

Cited by 6 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, cholera toxin (CT), LT, and dibutyryl-cyclic AMP all induce hypersecretion and impact the architecture of gastrointestinal epithelia in rodent small intestine 24 , while small intestinal biopsies of patients with acute cholera exhibit marked changes in the ultrastructure of the intestinal brush border, the major absorptive surface in the small intestine 25 , 26 , including shortening and disruption of the microvilli. Consistent with these observations, studies of young children less than two years of age in Bangladesh have specifically associated LT-producing ETEC with undernutrition 27 , suggesting that heat-labile toxin may exert effects on intestinal mucosa that extend beyond acute diarrheal illness.…”

Section: Introductionmentioning

confidence: 99%

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia

et al. 2022

View full text Add to dashboard Cite

Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children.

show abstract

Section: Introductionmentioning

confidence: 99%

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Notably, cholera toxin (CT), LT, and dibutyryl-cyclic AMP all induce hypersecretion and impact the architecture of gastrointestinal epithelia in rodent small intestine 24 , while small intestinal biopsies of patients with acute cholera exhibit marked changes in the ultrastructure of the intestinal brush border, the major absorptive surface in the small intestine 25,26 , including shortening and disruption 6/7/22 9:20:12 AM of the microvilli. Consistent with these observations, studies of young children less than two years of age in Bangladesh have specifically associated LT-producing ETEC with undernutrition 27 , suggesting that heat-labile toxin may exert effects on intestinal mucosa that extend beyond acute diarrheal illness.…”

Section: Introductionmentioning

confidence: 99%

EnterotoxigenicEscherichia coliheat-labile toxin drives enteropathic changes in small intestinal epithelia

Sheikh

Tumala

Vickers

et al. 2022

Preprint

View full text Add to dashboard Cite

Enterotoxigenic E. coli (ETEC), produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and are a common cause of diarrhea in children of resource-poor regions. ETEC have also been linked repeatedly to poorly understood sequelae including enteropathy, malnutrition, and growth impairment. While the cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their potential contribution to subsequent pathology is unclear. LT stimulates cellular cAMP production to activate protein kinase A (PKA) which phosphorylates cellular ion channels that drive export of salt and water into the intestinal lumen resulting in diarrhea. However, as PKA exhibits broad kinase activity and its activated catalytic subunits modulate transcription of many genes, we interrogated the transcriptional profiles of LT-treated small intestinal epithelia. These studies demonstrated toxin-induced changes in hundreds of genes including those required for biogenesis and function of the brush border, the major site absorption of nutrients, and suppression of a key transcription factor, HNF4, critical to differentiation of intestinal epithelia. Accordingly, LT treatment of intestinal epithelial cells significantly disrupted the absorptive microvillus architecture and altered transport of essential nutrients. In addition, challenge of neonatal mice with LT-producing ETEC recapitulated the architectural derangement of the brush border while maternal vaccination with LT prevented brush border disruption in ETEC-challenged neonatal mice. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to mitigate and prevent major sequelae including malnutrition that impact millions of young children.

show abstract

Structural and Functional Aspects of Cells in the Nasal Mucociliary System

Petruson¹,

Hansson²,

Karlsson³

1984

Archives of Otolaryngology - Head and Neck Surgery

View full text Add to dashboard Cite

\s=b\The regulation of the fluid balance of the mucus is important for a good function of the mucociliary system in the nose. The nasal glands and the goblet cells have been proposed to be the main source of fluid. Microvilli-equipped epithelial cells, ciliated and nonciliated, constituting 70% to 90% of the cells on the turbinates in the nose, are of importance for the regulation of the hydration of the mucus. These cells have the same characteristics as other fluid-secreting cells elsewhere in the body. They have microvilli, a terminal web, folding of the basolateral membrane, and numerous cell organelles. Blockage of the energy supply strongly reduces the fluid secretion.

show abstract

CYTOSKELETAL DISARRANGEMENT IN RAT INTESTINAL EPITHELIUM AFTER IN VIVO EXPOSURE TO SECRETAGOGUES

Cited by 6 publications

References 18 publications

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia

EnterotoxigenicEscherichia coliheat-labile toxin drives enteropathic changes in small intestinal epithelia

Structural and Functional Aspects of Cells in the Nasal Mucociliary System

Contact Info

Product

Resources

About