Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

Büller, Nikè V. J. A.; Rosekrans, Sanne; Westerlund, Jessica; Brink, Gijs R. van den

doi:10.1152/physiol.00003.2012

Cited by 52 publications

(56 citation statements)

References 43 publications

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“…These data suggest that subepithelial PDGFR␣ ϩ cells in murine colonic mucosa may be targets for Indian hedgehog, which is released from the colonic epithelium (42). Hedgehog signaling has an important role in maintaining homeostasis in the intestinal mucosa, but questions about its role remain unanswered (8). Finding a new target for hedgehog signaling might provide greater insight into the role of this pathway.…”

Section: Discussionmentioning

confidence: 94%

“…Htr3a and Htr3b expressions were much lower in PDGFR␣ ϩ cells than in other mucosal cells. Recently, mesenchymal PDGFR␣ ϩ cells in embryonic small intestine were reported to express hedgehog signaling molecules, Patched1 and the glioblastoma transcription factor 1 (Gli1) (44) and hedgehog signaling is expressed in colonic mesenchymal cells and contribute to maintenance of mucosal homeostasis (42,8). Therefore we probed the expression of two hedgehog signaling molecules (Ptch1 and Gli1).…”

Section: G829 Colonic Subepithelial Pdgfr␣ ϩ Cellsmentioning

confidence: 99%

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A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

Kurahashi

Nakano

Peri

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: Discussionmentioning

confidence: 94%

Section: G829 Colonic Subepithelial Pdgfr␣ ϩ Cellsmentioning

confidence: 99%

A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

Kurahashi

Nakano

Peri

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In contrast, in the intestine signaling is uniquely from the differentiated epithelial cells to the underlying mesenchyme. Here Hedgehog signaling regulates survival and expansion of the mesenchyme and in fact negatively regulates epithelial precursor cell proliferation (11).…”

Section: Signaling Pathways Involved In Esophageal Morphogenesismentioning

confidence: 99%

“…Thus Bmp4 is required for proper airway development after the initial specification of the tracheal primordium. The importance of Bmp4 in airway development may explain why the airways fail to develop properly in Shh-mutant mice since Bmp4 is one of the key mesenchymal targets of Hedgehog-Foxf1/Foxf2 signaling in the esophagus (42) and the intestine (11).…”

Section: The Morphogenetic Signaling Network Responsible For Gutairwamentioning

confidence: 99%

Esophageal development and epithelial homeostasis

Rosekrans

Baan

Muncan

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Rosekrans SL, Baan B, Muncan V, van den Brink GR. Esophageal development and epithelial homeostasis. Am J Physiol Gastrointest Liver Physiol 309: G216 -G228, 2015. First published July 2, 2015; doi:10.1152/ajpgi.00088.2015.-The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that lacks any metabolic, digestive, or absorptive function. The mucosa of the adult esophagus is covered by a multilayered squamous epithelium with a remarkable similarity to the epithelium of the skin despite the fact that these tissues originate from two different germ layers. Here we review the developmental pathways involved in the establishment of the esophagus and the way these pathways regulate gut-airway separation. We summarize current knowledge of the mechanisms that maintain homeostasis in esophageal epithelial renewal in the adult and the molecular mechanism of the development of Barrett's metaplasia, the precursor lesion to esophageal adenocarcinoma. Finally, we examine the ongoing debate on the hierarchy of esophageal epithelial precursor cells and on the presence or absence of a specific esophageal stem cell population. Together the recent insights into esophageal development and homeostasis suggest that the pathways that establish the esophagus during development also play a role in the maintenance of the adult epithelium. We are beginning to understand how reflux of gastric content and the resulting chronic inflammation can transform the squamous esophageal epithelium to columnar intestinal type metaplasia in Barrett's esophagus. esophagus; development; homeostasis; stem cell; endoderm THE WORD ESOPHAGUS IS DERIVED from the Greek words ε (oisein, to carry) and ␣␥ε (phagein, to eat). This description fits well with the functional role of the esophagus that mainly serves to "carry food" into the stomach. From the pharyngoesophageal junction, the esophagus passes through the mediastinum and diaphragm and connects to the cardia of the stomach at the gastroesophageal junction or Z-line. The pharyngoesophageal and gastroesophageal junctions anatomically overlap with the upper and lower esophageal sphincters. Both sphincters are closed except during swallowing to assure a unidirectional flow of esophageal content toward the stomach and to prevent reflux of gastric content into the esophagus. The relatively simple histology of the esophageal epithelium corresponds with the fact that the esophagus has no role other than to pass food through the thorax to the stomach. It does not play a known digestive, endocrine, or metabolic role and the epithelium consists of a simple stratified squamous epithelium, which provides a good protective layer against the unmodified food stream on its way to the stomach. Despite the perhaps somewhat prosaic functional role of the esophagus compared with other organs in the body, we feel that it is essential to gain a better understanding of the mechanisms that regulate normal esophageal homeo...

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“…33 Interestingly, it has been shown that together with a barrier-promoting effect, activation of the SHH pathway favors the immune quiescence of BBB by reducing the expression of pro-inflammatory cytokines and leukocyte transmigration. 33 In the gut, SHH signaling is necessary for the formation of villi during development and has homeostatic functions in the adult 34,35 indeed Hedgehog ligands, produced mainly by the epithelium, act on mesenchymal cells (smooth muscle cells, myofibroblast-like cells and pericytes located in the lamina propria) and they function as signals to assess epithelial barrier integrity. Our new data suggest an involvement of the SHH pathway also in the maintenance of the GVB but further investigation is required.…”

mentioning

confidence: 99%

Gene expression profile of endothelial cells during perturbation of the gut vascular barrier

et al. 2016

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It has been widely demonstrated that tolerance against gut microbiota is compartmentalized to mucosal sites where microbes mostly reside. How the commensal bacteria are excluded from the entrance into the blood stream via intestinal capillaries that are located beneath the gut epithelium was not clear. We recently described the existence of a new anatomical structure, the 'gut vascular barrier' (GVB), both in murine and human intestines that plays a fundamental role in avoiding indiscriminate trafficking of bacteria from the gut into the blood circulation. The vascular barrier integrity could be altered by Salmonella typhimurium, a pathogen capable of systemic dissemination, through the modulation of the Wnt/b-catenin signaling pathway. Here we have analyzed the differences in gut endothelial gene expression profiles during Salmonella infection and have identified some interesting characteristics of endothelial to mesenchymal transition. These findings add new insights in the gut-liver axis. The intestine is continuously exposed to a huge amount of foreign antigens, mostly food proteins and commensal microorganisms. These harmless antigens induce oral tolerance, which is however different when considering gut bacteria or food antigens. Tolerance to food proteins affects both local and systemic immune responses 1 indeed fed soluble antigens can gain access to the lymphatics to reach the mesenteric lymph nodes (mLN) 2 and the blood stream to reach the liver 3 where oral tolerance is established. By contrast, gut microbes are confined at mucosal sites by the mLNs that function like a firewall avoiding the spreading of intestinal microflora through the thoracic duct into the blood circulation. [4][5][6] Therefore at steady state the systemic immune system is left ignorant to the microbiota. Only during intestinal pathology bacteria can reach the liver that acts as a firewall preventing the bacteria from spreading to other systemic sites. 7 How the microbiota recirculates through the lymphatics has been widely studied, while how intestinal bacteria are excluded from the blood circulation was completely unexplored, even though it is known that intestinal capillaries are located just underneath the epithelial layer whereas the lymphatics are much deeper in the lamina propria.In our recent work, we hypothesized the existence of a barrier at the endothelial level, the 'gut vascular barrier' (GVB), 8 that similarly to the blood brain barrier (BBB) is able to control the type of antigens that can translocate into the blood stream and that is not permissive to bacterial penetration.Drawing a parallelism between the well-known BBB and the newly identified GVB many similarities can be found. Both are able to avoid the indiscriminate movement of molecules, cells and bacteria from blood to the brain parenchyma in the BBB and from the intestinal lumen into the blood circulation in the case of the GVB.

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Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

Cited by 52 publications

References 43 publications

A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

Esophageal development and epithelial homeostasis

Gene expression profile of endothelial cells during perturbation of the gut vascular barrier

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