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

Ranganathan P, Jayakumar C, Li DY, Ramesh G - J. Cell. Mol. Med. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, USA.

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UNC5B deletion exacerbates epithelial cells apoptosis. (A) Apoptosis of colonic cell following DSS colitis in WT and UNC5B heterozygous knockout mice was determined by TUNEL assay. Quantitative data for TUNEL-positive nuclei in five 40 × fields are given below. DSS induced a large increase in apoptotic cells in WT mice, which was further increased in UNC5B heterozygous knockout mice. *P < 0.001 versus water treated and #P < 0.05 versus other groups; N = 6–8; scale bar: 100 μM. (B) Pro-apoptotic gene expression was significantly increased in UNC5B+/− with DSS as compared WT mice or water-treated control mice. *P < 0.001 versus other groups; n = 5.
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fig06: UNC5B deletion exacerbates epithelial cells apoptosis. (A) Apoptosis of colonic cell following DSS colitis in WT and UNC5B heterozygous knockout mice was determined by TUNEL assay. Quantitative data for TUNEL-positive nuclei in five 40 × fields are given below. DSS induced a large increase in apoptotic cells in WT mice, which was further increased in UNC5B heterozygous knockout mice. *P < 0.001 versus water treated and #P < 0.05 versus other groups; N = 6–8; scale bar: 100 μM. (B) Pro-apoptotic gene expression was significantly increased in UNC5B+/− with DSS as compared WT mice or water-treated control mice. *P < 0.001 versus other groups; n = 5.

Mentions: Gene expression analysis showed that DSS induced a significant increase in the expression of inflammatory cytokines and chemokines in WT mice treated with DSS over water-treated mice, which was further increased in UNC5B−/+ mice treated with DSS (Fig. 5). Increased inflammation was associated with increased apoptosis in the colonic epithelial cells which was further increased in UNC5B−/+ mice treated with DSS (Fig. 6A). Consistent with increased apoptosis, the expression of several pro-apoptotic genes was significantly increased in UNC5B+/+ WT mice treated with DSS as compared to water-treated control, which was further increased in UNC5B+/− mice treated with DSS (Fig. 6B).


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

Ranganathan P, Jayakumar C, Li DY, Ramesh G - J. Cell. Mol. Med. (2014)

UNC5B deletion exacerbates epithelial cells apoptosis. (A) Apoptosis of colonic cell following DSS colitis in WT and UNC5B heterozygous knockout mice was determined by TUNEL assay. Quantitative data for TUNEL-positive nuclei in five 40 × fields are given below. DSS induced a large increase in apoptotic cells in WT mice, which was further increased in UNC5B heterozygous knockout mice. *P < 0.001 versus water treated and #P < 0.05 versus other groups; N = 6–8; scale bar: 100 μM. (B) Pro-apoptotic gene expression was significantly increased in UNC5B+/− with DSS as compared WT mice or water-treated control mice. *P < 0.001 versus other groups; n = 5.
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Related In: Results  -  Collection

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fig06: UNC5B deletion exacerbates epithelial cells apoptosis. (A) Apoptosis of colonic cell following DSS colitis in WT and UNC5B heterozygous knockout mice was determined by TUNEL assay. Quantitative data for TUNEL-positive nuclei in five 40 × fields are given below. DSS induced a large increase in apoptotic cells in WT mice, which was further increased in UNC5B heterozygous knockout mice. *P < 0.001 versus water treated and #P < 0.05 versus other groups; N = 6–8; scale bar: 100 μM. (B) Pro-apoptotic gene expression was significantly increased in UNC5B+/− with DSS as compared WT mice or water-treated control mice. *P < 0.001 versus other groups; n = 5.
Mentions: Gene expression analysis showed that DSS induced a significant increase in the expression of inflammatory cytokines and chemokines in WT mice treated with DSS over water-treated mice, which was further increased in UNC5B−/+ mice treated with DSS (Fig. 5). Increased inflammation was associated with increased apoptosis in the colonic epithelial cells which was further increased in UNC5B−/+ mice treated with DSS (Fig. 6A). Consistent with increased apoptosis, the expression of several pro-apoptotic genes was significantly increased in UNC5B+/+ WT mice treated with DSS as compared to water-treated control, which was further increased in UNC5B+/− mice treated with DSS (Fig. 6B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, USA.

Show MeSH
Related in: MedlinePlus