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HIF1α deficiency reduces inflammation in a mouse model of proximal colon cancer.

Mladenova DN, Dahlstrom JE, Tran PN, Benthani F, Bean EG, Ng I, Pangon L, Currey N, Kohonen-Corish MR - Dis Model Mech (2015)

Bottom Line: Microscopically, Hif1α(ΔIEC) mice had significantly less severe colon inflammation than Hif1α(F/F) mice.Molecular analysis showed reduced MIF expression and increased E-cadherin mRNA expression in the colon of sulindac-treated Hif1α(ΔIEC) mice.Taken together, HIF1α expression augments inflammation in the proximal colon of sulindac-treated mice, and AHR activation by sulindac might lead to the reduction of E-cadherin protein levels through the mitogen-activated protein kinase (MAPK) pathway.

View Article: PubMed Central - PubMed

Affiliation: Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, 2010, Australia.

No MeSH data available.


Related in: MedlinePlus

HIFα deficiency increases E-cadherin mRNA expression in the colon mucosa of Hif1αΔIEC mice. Q-PCR analysis for mRNA expression of E-cadherin (A), Slug (Snai2) (B), Snail (Snai1) (C), Twist1 (D), Twist2 (E), Myc (F), Axin2 (G) and Lgr5 (H) in the mucosal scrapings, whole biopsies and lesions harvested from the proximal colon of Hif1αΔIEC and Hif1αF/F mice treated with sulindac (Sul) or the control (Con) diet. Gene expression was normalised to that of Rpl19. Error bars indicate s.e.m. Star (*) indicates P<0.05. ΔIEC=Hif1αΔIEC, F/F=Hif1αF/F.
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DMM019000F4: HIFα deficiency increases E-cadherin mRNA expression in the colon mucosa of Hif1αΔIEC mice. Q-PCR analysis for mRNA expression of E-cadherin (A), Slug (Snai2) (B), Snail (Snai1) (C), Twist1 (D), Twist2 (E), Myc (F), Axin2 (G) and Lgr5 (H) in the mucosal scrapings, whole biopsies and lesions harvested from the proximal colon of Hif1αΔIEC and Hif1αF/F mice treated with sulindac (Sul) or the control (Con) diet. Gene expression was normalised to that of Rpl19. Error bars indicate s.e.m. Star (*) indicates P<0.05. ΔIEC=Hif1αΔIEC, F/F=Hif1αF/F.

Mentions: Q-PCR analyses showed that mRNA levels of E-cadherin were significantly higher in Hif1αΔIEC mice compared with those of Hif1αF/F mice (Fig. 4A). The increase was seen in mice that received either the control or the sulindac diet, and therefore, it was due to the loss of HIF1α in the colon epithelium. E-cadherin gene expression is repressed through EMT transcription factors, such as Snail, Slug and Twist (Batlle et al., 2000; Bolos et al., 2003; Cano et al., 2000; Hajra et al., 2002; Yang et al., 2008). However, no significant differences were observed in the expression of Snail, Slug or Twist between Hif1αF/F and Hif1αΔIEC mice (Fig. 4B-E).Fig. 4.


HIF1α deficiency reduces inflammation in a mouse model of proximal colon cancer.

Mladenova DN, Dahlstrom JE, Tran PN, Benthani F, Bean EG, Ng I, Pangon L, Currey N, Kohonen-Corish MR - Dis Model Mech (2015)

HIFα deficiency increases E-cadherin mRNA expression in the colon mucosa of Hif1αΔIEC mice. Q-PCR analysis for mRNA expression of E-cadherin (A), Slug (Snai2) (B), Snail (Snai1) (C), Twist1 (D), Twist2 (E), Myc (F), Axin2 (G) and Lgr5 (H) in the mucosal scrapings, whole biopsies and lesions harvested from the proximal colon of Hif1αΔIEC and Hif1αF/F mice treated with sulindac (Sul) or the control (Con) diet. Gene expression was normalised to that of Rpl19. Error bars indicate s.e.m. Star (*) indicates P<0.05. ΔIEC=Hif1αΔIEC, F/F=Hif1αF/F.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582097&req=5

DMM019000F4: HIFα deficiency increases E-cadherin mRNA expression in the colon mucosa of Hif1αΔIEC mice. Q-PCR analysis for mRNA expression of E-cadherin (A), Slug (Snai2) (B), Snail (Snai1) (C), Twist1 (D), Twist2 (E), Myc (F), Axin2 (G) and Lgr5 (H) in the mucosal scrapings, whole biopsies and lesions harvested from the proximal colon of Hif1αΔIEC and Hif1αF/F mice treated with sulindac (Sul) or the control (Con) diet. Gene expression was normalised to that of Rpl19. Error bars indicate s.e.m. Star (*) indicates P<0.05. ΔIEC=Hif1αΔIEC, F/F=Hif1αF/F.
Mentions: Q-PCR analyses showed that mRNA levels of E-cadherin were significantly higher in Hif1αΔIEC mice compared with those of Hif1αF/F mice (Fig. 4A). The increase was seen in mice that received either the control or the sulindac diet, and therefore, it was due to the loss of HIF1α in the colon epithelium. E-cadherin gene expression is repressed through EMT transcription factors, such as Snail, Slug and Twist (Batlle et al., 2000; Bolos et al., 2003; Cano et al., 2000; Hajra et al., 2002; Yang et al., 2008). However, no significant differences were observed in the expression of Snail, Slug or Twist between Hif1αF/F and Hif1αΔIEC mice (Fig. 4B-E).Fig. 4.

Bottom Line: Microscopically, Hif1α(ΔIEC) mice had significantly less severe colon inflammation than Hif1α(F/F) mice.Molecular analysis showed reduced MIF expression and increased E-cadherin mRNA expression in the colon of sulindac-treated Hif1α(ΔIEC) mice.Taken together, HIF1α expression augments inflammation in the proximal colon of sulindac-treated mice, and AHR activation by sulindac might lead to the reduction of E-cadherin protein levels through the mitogen-activated protein kinase (MAPK) pathway.

View Article: PubMed Central - PubMed

Affiliation: Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, 2010, Australia.

No MeSH data available.


Related in: MedlinePlus