Homeobox gene expression in the intestinal epithelium of adult mice.

Using a polymerase chain reaction-based strategy, we have detected the expression of nine different homeobox genes in adult mouse intestine. Included among these are the recently described intestine-specific Cdx-1 gene and a new, related gene, Cdx-2. Southern blot experiments show that Cdx-2 is present in a single copy in the mouse genome. Of several adult mouse tissues assayed, intestine was the only one that contained detectable levels of Cdx-2 mRNA. Expression of all nine homeobox genes in different regions of the intestine was quantitated by RNase protection analysis, which revealed a unique expression profile for each gene. These observations suggest that homeobox gene expression may play an important role in cellular differentiation in the adult intestine.     

Live and let die in the intestinal epithelium

The intestinal epithelium is a relatively simple developmental system and a prime example of tissue renewal from a source of multipotent stem cells. Throughout adulthood, intestinal epithelial proliferation, cell-fate specification and differentiation are coupled to migration in discrete units known as crypts of Lieberkühn. Physically guided by Eph receptors and their ligands, the ephrins, stem cell progeny transit through the proliferation/differentiation switch, and Notch diversifies their subsequent fates. Wnt signalling appears to control most of these events.     

Iron Imports. V. Transport of iron through the intestinal epithelium

Iron absorption across the brush-border membrane requires divalent metal transporter 1 (DMT1), whereas ferroportin (FPN) and hephaestin are required for exit across the basolateral membrane. However, how iron passes across the enterocyte is poorly understood. Both chaperones and transcytosis have been postulated to account for intracellular iron transport. With iron feeding, DMT1 undergoes endocytosis and FPN translocates from the apical cytosol to the basolateral membrane. The fluorescent metallosensor calcein offered to the basolateral surface of enterocytes is found in endosomes in the apical compartment, and its fluorescence is quenched when iron is offered to the apical surface. These experiments are consistent with vesicular iron transport as a possible pathway for intracellular iron transport.     

Lymphoid cells in chicken intestinal epithelium

The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule leucocytes of previous authors. The numbers of all cell types increased with age. Correlation was found between the number of small lymphocytes and large lymphoid cells, but not between granular cells and either of the other two. A hypothesis is proposed, assigning these cells with a function in mucosal immunity.     

The crypt cycle. Crypt and villus production in the adult intestinal epithelium.

We propose a model for the growth of individual crypts that is able to account for the observed changes in the number of cells in crypts under normal conditions, after irradiation, and after 30% resection. Parameter values for this model are estimated both for mouse and man, and detailed predictions of crypt growth rates are made. This model does not predict a steady-state crypt size; rather it suggests that crypts grow until they bifurcate. We therefore propose a crypt cycle (analogous to the cell cycle) and present evidence that most if not all crypts in the adult mouse are cycling asynchronously and independently. This evidence consists of four experiments that indicate that branching crypts are randomly distributed over the intestinal epithelium, that the plane of bifurcation of branching crypts is randomly oriented with respect to the villus base, and that the size distribution of crypts is consistent with an expanding crypt population. We also report for the first time evidence of villus production in the adult mouse intestinal epithelium. We conclude that the crypt and villus populations in the adult mouse are not in a steady state.     

肠上皮与肠道微生物相互作用研究进展

肠道不仅是消化和吸收的主要场所,也是机体重要的免疫器官。人类肠道中存在着超过百万亿的微生物,其在漫长的自然选择及共同进化中与宿主形成了紧密的共生关系。肠上皮是先天免疫的一个组成部分,通过各种黏膜保护屏障将肠腔内容物与机体内环境分隔开。各种肠上皮细胞相互协调维持肠道内稳态,并与肠道微生物、肠黏膜免疫系统共同形成抵御肠腔内有害抗原的第一道防线。肠上皮作为肠道微生物和肠黏膜免疫系统相互作用的枢纽,在黏膜免疫防御体系中具有重要作用,本文就肠上皮与肠道微生物之间的相互作用进行综述,旨在深入理解肠上皮,为探索肠道相关疾病的治疗提供新思路。     

Autophagy in the intestinal epithelium is not involved in the pathogenesis of intestinal tumors

Autophagy has been demonstrated to be associated with the pathogenesis of cancer, but no consensus has been reached about its precise role. Therefore, we investigated whether autophagy in the intestinal epithelium is involved in the pathogenesis of intestinal tumors. To evaluate the relationship between autophagy and intestinal tumors, GFP-LC3-APC(min/+) mice were generated by mating GFP-LC3 transgenic mice with APC(min/+) mice. Autophagy was weakly induced in the intestinal polyp regions of the mice in comparison to their non-polyp regions. Under starved conditions, autophagy was not induced in the polyp regions, whereas it was observed in the non-polyp regions. Then, to examine whether a lack of autophagy in the intestinal epithelium enhances the induction of intestinal tumor, Atg7flox/flox:vil-cre-APC(min/+) mice, in which Atg7 had been conditionally deleted in the intestinal epithelium, were generated by mating Atg7flox/flox:vil-cre mice with APC(min/+) mice. However, there was no significant difference in the number of intestinal polyps between the Atg7flox/flox:vil-cre-APC(min/+) and the corresponding control Atg7flox/flox-APC(min/+) mice. These results indicate that autophagy in the intestinal epithelium is not involved in the pathogenesis of intestinal tumors, and future research should focus on regulating autophagy as a form of cancer therapy.     

Murine intestinal organoids resemble intestinal epithelium in their microRNA profiles

Intestinal organoids were established as an ex vivo model of the intestinal epithelium. We investigated whether organoids resemble the intestinal epithelium in their microRNA (miRNA) profiles. Total RNA samples were obtained from crypt and villus fractions in murine intestine and from cultured organoids. Microarray analysis showed that organoids largely resembled intestinal epithelial cells in their miRNA profiles. In silico prediction followed by qRT-PCR suggested that six genes are regulated by corresponding miRNAs along the crypt-villus axis, suggesting miRNA regulation of epithelial cell renewal in the intestine. However, such expression patterns of miRNAs and their target mRNAs were not reproduced during organoids maturation. This might be due to lack of luminal factors and endocrine, nervous, and immune systems in organoids and different cell populations between in vivo epithelium and organoids. Nevertheless, we propose that intestinal organoids provide a useful in vitro model to investigate miRNA expression in intestinal epithelial cells.     

Glucose absorption by the interposed colon segment after intestinal resection.

One of the proposed surgical treatments of Short Bowel Syndrome is the interposition of a distal colon segment between two portions of the remnant small intestine. This method proved to reverse the nutritional disorders caused by this morbid entity. Surgical technique consisted in an 80% small bowel resection and the interposition of a 3 cm segment of distal colon between the remaining jejunum and ileum. After 70 days, the animals were reoperated and the interposed and the distal colon were isolated and tied. By using the method of rapid and successive absorptions of a glucose solution through the intestinal lumen, the relations between the absorption curves of the interposed and the normal colon could be drawn. Results show that the interposed colon segment absorbs more glucose (mean = 1.43 +/- 1.16 mg/dl) than the distal colon (mean = 0.37 +/- 0.29 mg/dl) and that its absorption pattern is similar to the small bowel rather than the colon. These results allow the use of this method for further studies in which the interposed colon adaptation is studied with other nutrients and/or under specific conditions.     

Proteus adhesion to intestinal epithelium

The adhesive properties of Proteus strains isolated from different sources have been studied under conditions similar to the real interaction of microorganisms with the epithelial cells of intestine. A comparison of the adhesive properties of Proteus and of colon Bacillus has shown that the value of the strong adhesion to the mucosa of Proteus isolated under enterocolitis at the same bulk concentrations of the infectious suspension is 2-3 order less than that of E. coli. The adhesion of Proteus to the surface of epithelial cells begins at bulk concentrations exceeding those for the colon Bacillus by 3-4 orders. Besides, a toxic effect of number of freshly isolated Proteus strains on the epithelial cells of intestine mucosa is observed. Strains isolated from patients with diarrhea and from environment differed from each other in the studied criteria. A conclusion is drawn that at the initial stage of the interaction with the intestine mucosa the Proteus strains differ considerably from the indigenous strain of the colon Bacillus in the ability to colonize the epithelial surface.