Notch Signaling Promotes Intestinal Crypt Fission in the Infant Rat

Cummins, Adrian G.; Woenig, Joshua A.; Donato, Rino P.; Proctor, Simon J.; Howarth, Gordon S.; Grover, Phulwinder K.

doi:10.1007/s10620-012-2422-y

Cited by 9 publications

(3 citation statements)

References 24 publications

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“…No. D5942), a γ-secretase inhibitor, 1 h before hypoxia to investigate the effect of Notch blockade in vivo [29], [30]. Control rats were subjected to hypoxia without DAPT pretreatment (n = 3).…”

Section: Methodsmentioning

confidence: 99%

Notch-1 Signaling Regulates Microglia Activation via NF-κB Pathway after Hypoxic Exposure In Vivo and In Vitro

et al. 2013

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Neuroinflammation mediated by the activated microglia is suggested to play a pivotal role in the pathogenesis of hypoxic brain injury; however, the underlying mechanism of microglia activation remains unclear. Here, we show that the canonical Notch signaling orchestrates microglia activation after hypoxic exposure which is closely associated with multiple pathological situations of the brain. Notch-1 and Delta-1 expression in primary microglia and BV-2 microglial cells was significantly elevated after hypoxia. Hypoxia-induced activation of Notch signaling was further confirmed by the concomitant increase in the expression and translocation of intracellular Notch receptor domain (NICD), together with RBP-Jκ and target gene Hes-1 expression. Chemical inhibition of Notch signaling with N-[N-(3,5-difluorophenacetyl)-1-alany1- S-phenyglycine t-butyl ester (DAPT), a γ-secretase inhibitor, effectively reduced hypoxia-induced upregulated expression of most inflammatory mediators. Notch inhibition also reduced NF-κB/p65 expression and translocation. Remarkably, Notch inhibition suppressed expression of TLR4/MyD88/TRAF6 pathways. In vivo, Notch signaling expression and activation in microglia were observed in the cerebrum of postnatal rats after hypoxic injury. Most interestingly, hypoxia-induced upregulation of NF-κB immunoexpression in microglia was prevented when the rats were given DAPT pretreatment underscoring the interrelationship between Notch signaling and NF-κB pathways. Taken together, we conclude that Notch signaling is involved in regulating microglia activation after hypoxia partly through the cross talk between TLR4/MyD88/TRAF6/NF-κB pathways. Therefore, Notch signaling may serve as a prospective target for inhibition of microglia activation known to be implicated in brain damage in the developing brain.

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Section: Methodsmentioning

confidence: 99%

Notch-1 Signaling Regulates Microglia Activation via NF-κB Pathway after Hypoxic Exposure In Vivo and In Vitro

et al. 2013

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“…We have shown a nadir of apoptosis in crypts at the peak of signaling in rats at 14 days of life [26], and recorded zero apoptosis in human infants up to 3-4 years of age before rising exponentially until late teenage years [20]. Blockade of notch signalling increased apoptosis in crypts in infant rats [31]. We speculate that Notch signalling is Wnt dependent.…”

Section: Age Dependence Of Wnt2b Wnt3 and R-spondin-1 Protein Expression In Ratsmentioning

confidence: 96%

Wnt2b, Wnt3, and R-Spondin-1 Promote β-Catenin Signaling in the Small Intestine during Infancy

M¹,

P²,

J³

et al. 2021

Insights Stem Cell Res Ther

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“…The evidence supporting this notion is that when intestinal epithelial stem cells are co-cultured in vitro with intestinal subepithelial myofibroblasts, the enteroids are larger and have improved viability 13 . In addition, although the source of these factors is not always limited to the stroma, there are reports concerning the relationship of crypt fission with differentiation/proliferation signals 5,[14][15][16] and inflammatory diseases 17 in rodents and humans. In summary, these indications of mutual dependence suggest that physical interaction between epithelial cells and stromal cells is needed to complete the intestinal structure.…”

mentioning

confidence: 99%

Histopathological evaluation of crypt fission during intestinal development in neonatal mice

Yamazaki¹,

Fujii

Watanabe³

et al. 2020

J Toxicol Pathol

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Pathological evaluation of juvenile toxicity studies requires the understanding of normal tissue development at different ages. Here, we report the morphological features of the neonatal mouse intestine, focusing on crypt fission. Postnatal day (PND) 7 and 14 mice showed fewer crypts and less mature epithelial morphology compared to PND 21 and 28. Crypt fission occurred in three stages: 1) flattening of the crypt base into a skirt shape, 2) penetration of myofibroblasts into the crypt base center, and 3) complete separation of a single crypt into two daughter crypts. The ratio of crypt fission to total number of crypts was the highest at PND 14 and 7 in the jejunum and colon, respectively. Crypt fission, a key phenomenon for balance or imbalance in epithelial cell hierarchy, including stem and differentiated cells, is related to tissue injury repair and tumorigenesis. Therefore, examining crypt fission can provide valuable insights into current conditions of intestine.

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Notch Signaling Promotes Intestinal Crypt Fission in the Infant Rat

Abstract: We conclude that Notch signaling promotes crypt fission and growth of the intestine by maintaining low apoptosis of crypt cells.

Cited by 9 publications

References 24 publications

Notch-1 Signaling Regulates Microglia Activation via NF-κB Pathway after Hypoxic Exposure In Vivo and In Vitro

Notch-1 Signaling Regulates Microglia Activation via NF-κB Pathway after Hypoxic Exposure In Vivo and In Vitro

Wnt2b, Wnt3, and R-Spondin-1 Promote β-Catenin Signaling in the Small Intestine during Infancy

Histopathological evaluation of crypt fission during intestinal development in neonatal mice

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