High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children.
Enteropathies such as Crohn's disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired i...
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ftdoajarticles:oai:doaj.org/article:f099c64b2ef44fdfa57eed722fde994b 2023-05-15T15:16:20+02:00 High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. Sana Syed Vincenzo Dinallo Najeeha T Iqbal Laura Di Iorio Davide Di Fusco Shan Guleria Beatrice C Amadi Kamran Sadiq Christopher Moskaluk S Asad Ali Paul Kelly Giovanni Monteleone 2018-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006224 https://doaj.org/article/f099c64b2ef44fdfa57eed722fde994b EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5819826?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006224 https://doaj.org/article/f099c64b2ef44fdfa57eed722fde994b PLoS Neglected Tropical Diseases, Vol 12, Iss 2, p e0006224 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006224 2022-12-31T16:29:37Z Enteropathies such as Crohn's disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired inflammatory disease of the small intestine (SI), which is associated with linear growth disruption, cognitive deficits, and reduced oral vaccine responsiveness in children <5 y in resource-poor countries. We aimed to characterize EE inflammatory pathways by determining SMAD7 and p-SMAD2,3 levels (using Western blotting) in EE duodenal biopsies (N = 19 children, 7 from Pakistan, 12 from Zambia) and comparing these with healthy controls (Ctl) and celiac disease (CD) patients from Italy. Densitometric analysis of immunoblots showed that EE SI biopsies expressed higher levels of both SMAD7 (mean±SD in arbitrary units [a.u.], Ctl = 0.47±0.20 a.u., EE = 1.13±0.25 a.u., p-value = 0.03) and p-SMAD2,3 (mean±SD, Ctl = 0.38±0.14 a.u., EE = 0.60±0.10 a.u., p-value = 0.03). Immunohistochemistry showed that, in EE, SMAD7 is expressed in both the epithelium and in mononuclear cells of the lamina propria (LP). In contrast, p-SMAD3 in EE is expressed much more prominently in epithelial cells than in the LP. The high SMAD7 immunoreactivity and lack of p-SMAD3 expression in the LP suggests defective TGF-β signaling in the LP in EE similar to a previously reported SMAD7-mediated inflammatory pathway in refractory CD and Crohn's disease. However, Western blot densitometry showed elevated p-SMAD2,3 levels in EE, possibly suggesting a different inflammatory pathway than Crohn's disease but more likely reflecting cumulative protein expression from across all compartments of the mucosa as opposed to the LP alone. Further studies are needed to substantiate these preliminary results and to illustrate the relationship between SMAD proteins, TGF-β signaling, and inflammatory cytokine production, all of which may be potential therapeutic targets. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 2 e0006224 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Sana Syed Vincenzo Dinallo Najeeha T Iqbal Laura Di Iorio Davide Di Fusco Shan Guleria Beatrice C Amadi Kamran Sadiq Christopher Moskaluk S Asad Ali Paul Kelly Giovanni Monteleone High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Enteropathies such as Crohn's disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired inflammatory disease of the small intestine (SI), which is associated with linear growth disruption, cognitive deficits, and reduced oral vaccine responsiveness in children <5 y in resource-poor countries. We aimed to characterize EE inflammatory pathways by determining SMAD7 and p-SMAD2,3 levels (using Western blotting) in EE duodenal biopsies (N = 19 children, 7 from Pakistan, 12 from Zambia) and comparing these with healthy controls (Ctl) and celiac disease (CD) patients from Italy. Densitometric analysis of immunoblots showed that EE SI biopsies expressed higher levels of both SMAD7 (mean±SD in arbitrary units [a.u.], Ctl = 0.47±0.20 a.u., EE = 1.13±0.25 a.u., p-value = 0.03) and p-SMAD2,3 (mean±SD, Ctl = 0.38±0.14 a.u., EE = 0.60±0.10 a.u., p-value = 0.03). Immunohistochemistry showed that, in EE, SMAD7 is expressed in both the epithelium and in mononuclear cells of the lamina propria (LP). In contrast, p-SMAD3 in EE is expressed much more prominently in epithelial cells than in the LP. The high SMAD7 immunoreactivity and lack of p-SMAD3 expression in the LP suggests defective TGF-β signaling in the LP in EE similar to a previously reported SMAD7-mediated inflammatory pathway in refractory CD and Crohn's disease. However, Western blot densitometry showed elevated p-SMAD2,3 levels in EE, possibly suggesting a different inflammatory pathway than Crohn's disease but more likely reflecting cumulative protein expression from across all compartments of the mucosa as opposed to the LP alone. Further studies are needed to substantiate these preliminary results and to illustrate the relationship between SMAD proteins, TGF-β signaling, and inflammatory cytokine production, all of which may be potential therapeutic targets. |
format |
Article in Journal/Newspaper |
author |
Sana Syed Vincenzo Dinallo Najeeha T Iqbal Laura Di Iorio Davide Di Fusco Shan Guleria Beatrice C Amadi Kamran Sadiq Christopher Moskaluk S Asad Ali Paul Kelly Giovanni Monteleone |
author_facet |
Sana Syed Vincenzo Dinallo Najeeha T Iqbal Laura Di Iorio Davide Di Fusco Shan Guleria Beatrice C Amadi Kamran Sadiq Christopher Moskaluk S Asad Ali Paul Kelly Giovanni Monteleone |
author_sort |
Sana Syed |
title |
High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. |
title_short |
High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. |
title_full |
High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. |
title_fullStr |
High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. |
title_full_unstemmed |
High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children. |
title_sort |
high smad7 and p-smad2,3 expression is associated with environmental enteropathy in children. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006224 https://doaj.org/article/f099c64b2ef44fdfa57eed722fde994b |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 2, p e0006224 (2018) |
op_relation |
http://europepmc.org/articles/PMC5819826?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006224 https://doaj.org/article/f099c64b2ef44fdfa57eed722fde994b |
op_doi |
https://doi.org/10.1371/journal.pntd.0006224 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
2 |
container_start_page |
e0006224 |
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1766346630093602816 |