Epithelial down-regulation of the miR-200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition

Shameer J. Mehta, Amy Lewis, Anke Nijhuis, Rosemary Jeffery, Paolo Biancheri, Antonio Di Sabatino, Roger Feakins, Andrew Silver, James Oliver Lindsay

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to the mesenchymal cell pool in CD fibrosis remains obscure. The miR-200 family regulates fibrosis-related EMT in organs other than the gut. E-cadherin, cytokeratin-18 and vimentin expression was assessed using immunohistochemistry on paired strictured (SCD) and non-strictured (NSCD) ileal CD resections and correlated with fibrosis grade. MiR-200 expression was measured in paired SCD and NSCD tissue compartments using laser capture microdissection and RT-qPCR. Serum miR-200 expression was also measured in healthy controls and CD patients with stricturing and non-stricturing phenotypes. Extra-epithelial cytokeratin-18 staining and vimentin-positive epithelial staining were significantly greater in SCD samples (P = 0.04 and P = 0.03, respectively). Cytokeratin-18 staining correlated positively with subserosal fibrosis (P < 0.001). Four miR-200 family members were down-regulated in fresh SCD samples (miR-141, P = 0.002; miR-200a, P = 0.002; miR-200c, P = 0.001; miR-429; P = 0.004); miR-200 down-regulation in SCD tissue was localised to the epithelium (P = 0.001-0.015). The miR-200 target ZEB1 was up-regulated in SCD samples (P = 0.035). No difference in serum expression between patient groups was observed. Together, these observations suggest the presence of EMT in CD strictures and implicate the miR-200 family as regulators. Functional studies to prove this relationship are now warranted.

Original languageEnglish
JournalJournal of Cellular and Molecular Medicine
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Epithelial-Mesenchymal Transition
Crohn Disease
Keratin-18
Down-Regulation
Fibrosis
Vimentin
Staining and Labeling
Ileal Diseases
Laser Capture Microdissection
Cadherins
Serum
Extracellular Matrix
Pathologic Constriction
Epithelium
Immunohistochemistry
Phenotype

Keywords

  • Crohn's disease
  • epithelial to mesenchymal transition
  • fibrosis
  • miR-200 family

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Epithelial down-regulation of the miR-200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition. / Mehta, Shameer J.; Lewis, Amy; Nijhuis, Anke; Jeffery, Rosemary; Biancheri, Paolo; Di Sabatino, Antonio; Feakins, Roger; Silver, Andrew; Lindsay, James Oliver.

In: Journal of Cellular and Molecular Medicine, 01.01.2018.

Research output: Contribution to journalArticle

Mehta, Shameer J. ; Lewis, Amy ; Nijhuis, Anke ; Jeffery, Rosemary ; Biancheri, Paolo ; Di Sabatino, Antonio ; Feakins, Roger ; Silver, Andrew ; Lindsay, James Oliver. / Epithelial down-regulation of the miR-200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition. In: Journal of Cellular and Molecular Medicine. 2018.
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abstract = "Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to the mesenchymal cell pool in CD fibrosis remains obscure. The miR-200 family regulates fibrosis-related EMT in organs other than the gut. E-cadherin, cytokeratin-18 and vimentin expression was assessed using immunohistochemistry on paired strictured (SCD) and non-strictured (NSCD) ileal CD resections and correlated with fibrosis grade. MiR-200 expression was measured in paired SCD and NSCD tissue compartments using laser capture microdissection and RT-qPCR. Serum miR-200 expression was also measured in healthy controls and CD patients with stricturing and non-stricturing phenotypes. Extra-epithelial cytokeratin-18 staining and vimentin-positive epithelial staining were significantly greater in SCD samples (P = 0.04 and P = 0.03, respectively). Cytokeratin-18 staining correlated positively with subserosal fibrosis (P < 0.001). Four miR-200 family members were down-regulated in fresh SCD samples (miR-141, P = 0.002; miR-200a, P = 0.002; miR-200c, P = 0.001; miR-429; P = 0.004); miR-200 down-regulation in SCD tissue was localised to the epithelium (P = 0.001-0.015). The miR-200 target ZEB1 was up-regulated in SCD samples (P = 0.035). No difference in serum expression between patient groups was observed. Together, these observations suggest the presence of EMT in CD strictures and implicate the miR-200 family as regulators. Functional studies to prove this relationship are now warranted.",
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AU - Lindsay, James Oliver

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AB - Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to the mesenchymal cell pool in CD fibrosis remains obscure. The miR-200 family regulates fibrosis-related EMT in organs other than the gut. E-cadherin, cytokeratin-18 and vimentin expression was assessed using immunohistochemistry on paired strictured (SCD) and non-strictured (NSCD) ileal CD resections and correlated with fibrosis grade. MiR-200 expression was measured in paired SCD and NSCD tissue compartments using laser capture microdissection and RT-qPCR. Serum miR-200 expression was also measured in healthy controls and CD patients with stricturing and non-stricturing phenotypes. Extra-epithelial cytokeratin-18 staining and vimentin-positive epithelial staining were significantly greater in SCD samples (P = 0.04 and P = 0.03, respectively). Cytokeratin-18 staining correlated positively with subserosal fibrosis (P < 0.001). Four miR-200 family members were down-regulated in fresh SCD samples (miR-141, P = 0.002; miR-200a, P = 0.002; miR-200c, P = 0.001; miR-429; P = 0.004); miR-200 down-regulation in SCD tissue was localised to the epithelium (P = 0.001-0.015). The miR-200 target ZEB1 was up-regulated in SCD samples (P = 0.035). No difference in serum expression between patient groups was observed. Together, these observations suggest the presence of EMT in CD strictures and implicate the miR-200 family as regulators. Functional studies to prove this relationship are now warranted.

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