UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis

Punithavathi Ranganathan, Calpurnia Jayakumar, Dean Y. Li, Ganesan Ramesh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The netrin-1 administration or overexpression is known to protect colon from acute colitis. However, the receptor that mediates netrin-1 protective activities in the colon during colitis remains unknown. We tested the hypothesis that UNC5B receptor is a critical mediator of protective function of netrin-1 in dextran sodium sulfate (DSS)-induced colitis using mice with partial deletion of UNC5B receptor. DSS colitis was performed in mice with partial genetic UNC5B deficiency (UNC5B+/- mice) or wild-type mice to examine the role of endogenous UNC5B. These studies were supported by in vitro models of DSS-induced apoptosis in human colon epithelial cells. WT mice developed colitis in response to DSS feeding as indicated by reduction in bw, reduction in colon length and increase in colon weight. These changes were exacerbated in heterozygous UNC5B knockout mice treated with DSS. Periodic Acid-Schiff stained section shows damages in colon epithelium and mononuclear cell infiltration in WT mice, which was further increased in UNC5B heterozygous knockout mice. This was associated with large increase in inflammatory mediators such as cytokine and chemokine expression and extensive apoptosis of epithelial cells in heterozygous knockout mice as compared to WT mice. Overexpression of UNC5B human colon epithelial cells suppressed DSS-induced apoptosis and caspase-3 activity. Moreover, DSS induced large amount of netrin-1 and shRNA mediated knockdown of netrin-1 induction exacerbated DSS-induced epithelial cell apoptosis. Our results suggest that UNC5B is a critical mediator of cell survival in response to stress in colon.

Original languageEnglish (US)
Pages (from-to)1290-1299
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume18
Issue number7
DOIs
StatePublished - Jul 2014

Fingerprint

Dextran Sulfate
Colitis
Colon
Epithelial Cells
Apoptosis
Knockout Mice
Periodic Acid
Chemokines
Caspase 3
Small Interfering RNA
Cell Survival
Epithelium
Cytokines
Weights and Measures
netrin-1

Keywords

  • Apoptosis
  • DSS colitis
  • Inflammatory bowel disease
  • Netrin-1
  • UNC5B

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis. / Ranganathan, Punithavathi; Jayakumar, Calpurnia; Li, Dean Y.; Ramesh, Ganesan.

In: Journal of Cellular and Molecular Medicine, Vol. 18, No. 7, 07.2014, p. 1290-1299.

Research output: Contribution to journalArticle

Ranganathan, Punithavathi ; Jayakumar, Calpurnia ; Li, Dean Y. ; Ramesh, Ganesan. / UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis. In: Journal of Cellular and Molecular Medicine. 2014 ; Vol. 18, No. 7. pp. 1290-1299.
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