ER stress induces epithelial differentiation in the mouse oesophagus

Rosekrans, Sanne; Heijmans, Jarom; Büller, Nikè V. J. A.; Westerlund, Jessica; Lee, Amy; Muncan, Vanesa; Brink, Gijs R. van den

doi:10.1136/gutjnl-2013-306347

Cited by 29 publications

(27 citation statements)

References 25 publications

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“…Changes of ER morphology can occur without ER stress (English and Voeltz, 2013), and some molecular actors that sign ER stress are not detected in Elp3cKO cortices. Indeed, UPR also works as a physiological homeostat that balances the cell's protein folding capacity with its needs and recent works support its active contribution to cell differentiation in distinct tissues (Heijmans et al, 2013;Rosekrans et al, 2015). We found that exacerbated transduction through the PERK-eiF2a UPR branch-also used by differentiating intestinal stem cells (Heijmans et al, 2013)-interferes with cortical neurogenesis in Elp3cKO embryos.…”

Section: Dynamic Regulation Of Upr Controls Neurogenesis In the Develmentioning

confidence: 53%

A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis

et al. 2015

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The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs), whose asymmetric division gives birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Here we show that interfering with codon translation speed triggers ER stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as a physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a contribution of UPR to cell fate acquisition during mammalian brain development.

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Section: Dynamic Regulation Of Upr Controls Neurogenesis In the Develmentioning

confidence: 53%

A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis

et al. 2015

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“…In another study, Ah1-Cre mediated GRP78 knockout in intestine led to induction of ER stress, loss of selfrenewal capacity and rapid repopulation of wild-type stem cells (Heijmans et al, 2013). This same study also showed Ah1-Cre activity in esophagus, and GRP78 null esophageal epithelial cells lost their proliferative capacity and were replaced by unrecombined GRP78-positive cells (Rosekrans et al, 2014).…”

Section: Intestine and Esophagusmentioning

confidence: 77%

Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis

2015

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The endoplasmic reticulum (ER) is a cellular organelle where secretory and membrane proteins, as well as lipids, are synthesized and modified. When cells are subjected to ER stress, an adaptive mechanism referred to as the Unfolded Protein Response (UPR) is triggered to allow the cells to restore homeostasis. Evidence has accumulated that the UPR pathways provide specialized and unique roles in diverse development and metabolic processes. The glucose regulated proteins (GRPs) are traditionally regarded as ER proteins with chaperone and calcium binding properties. The GRPs are constitutively expressed at basal levels in all organs, and as stress-inducible ER chaperones, they are major players in protein folding, assembly and degradation. This conventional concept is augmented by recent discoveries that GRPs can be actively translocated to other cellular locations such as the cell surface, where they assume novel functions that regulate signaling, proliferation, apoptosis and immunity. Recent construction and characterization of mouse models where the gene encoding for the UPR components and the GRPs is genetically altered provide new insights on the physiological contribution of these proteins in vivo. This review highlights recent progress towards the understanding of the role of the UPR and two major GRPs (GRP78 and GRP94) in regulating homeostasis of organs arising from the endoderm, mesoderm and ectoderm. GRP78 and GRP94 exhibit shared and unique functions, and in specific organs their depletion elicits adaptive responses with physiological consequences.

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“…Consistent with this, the small intestine, which contains high numbers of Paneth cells, has higher baseline levels of UPR-related gene expression than the colon [9]. The UPR is not only of importance to the function of differentiated IEC subtypes but also gut stem cells in general as ER stress and UPR induction are critical to such cells in the intestine [10 ▪ ] and oesophagus [11]. Given these broad biologic effects and evidence that UPR-related genetic risk loci are associated with inflammatory bowel disease (IBD), it is important to understand how these pathways operate in the maintenance of intestinal homeostasis and disease.…”

Section: Introductionmentioning

confidence: 89%

Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease

Hosomi

Kaser

Blumberg

2015

Current Opinion in Gastroenterology

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Purpose of review The purpose of this study is to provide an overview of the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in inflammatory bowel disease (IBD). Recent findings Human genetic studies have identified several UPR-related genes and autophagy-related genes as IBD risk loci. Impairment of each branch of the UPR causes spontaneous enteritis or creates higher susceptibility for intestinal inflammation in model systems. Deficiency of either UPR or autophagy in small intestinal epithelial cells promotes each other’s compensatory engagement, which is especially prominent in Paneth cells such that, in the absence of both, severe spontaneous enteritis emerges. Summary Interactions between the UPR and autophagy exhibit critical synergistic interactions within the intestinal epithelium and especially Paneth cells that are of considerable importance to the maintenance of homeostasis. When dysfunctional in the Paneth cell, spontaneous inflammation can emerge that may extend beyond the epithelium providing direct experimental evidence that subsets of Crohn’s disease may emanate from primary Paneth cell disturbances.

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ER stress induces epithelial differentiation in the mouse oesophagus

Abstract: These results show that ER stress induces epithelial differentiation in precursor cells in the oesophageal epithelium. This UPR induced differentiation may serve as a quality control mechanism that protects against oesophageal cancer development.

Cited by 29 publications

References 25 publications

A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis

A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis

Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis

Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease

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