Role of epithelial-mesenchymal interactions in the ontogenesis of intestinal brush-border enzymes

Kédinger, Michèle; Simon, Patricia; Grenier, J F; Haffen, K

doi:10.1016/0012-1606(81)90191-3

Cited by 102 publications

(53 citation statements)

References 25 publications

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“…In chronic uremia both increased and decreased activity of various disaccharidases has been demonstrated [2,3,5,21]. The different results of the acute and chronic uremia could also be due to different composition of the diets and to different length of the observation periods [22][23][24], The short uremic period in our study, compared to that of chronic uremia, could be one reason for the unaltered disaccharidase activity in the uremic group in our study.…”

Section: Discussionmentioning

confidence: 65%

Small Intestinal Peptidases and Disaccharidases in Rats with Acute Uremia

Magnusson

Sjöström²,

Norén³

et al. 1991

Nephron

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Acute uremia was induced in rats with temporary clamping of the left renal pedicle and contralateral nephrectomy. Jejunal peptidase activities (aminopeptidase N, dipeptidyl peptidase IV and aminopeptidase A), disaccharidase activities (maltase, sucrase, lactase and trehalase) and morphology were studied. A significant (p < 0.05) increase in aminopeptidase N activity and a positive correlation between aminopeptidase N activity and serum urea was found in the uremic rats. The other peptidase activities showed a slight increase in the uremic rats. A shortening of the microvilli of the small intestinal epithelial cells in the uremic rats was seen by electron microscopy. The disaccharidase activities were unaltered. This study shows the presence of functional alterations in the small intestine in rats with acute uremia. The observations are also compatible with different regulation mechanisms for the brush border peptidases and disaccharidases.

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Section: Discussionmentioning

confidence: 65%

Small Intestinal Peptidases and Disaccharidases in Rats with Acute Uremia

Magnusson

Sjöström²,

Norén³

et al. 1991

Nephron

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“…In these studies, it was not possible to decide to what extent non-epithelial cells were required for the response. Epithelial-mesenchymal interactions are known to play an important role in the differentiation of brush-border enzymes during development (Kedinger et al, 1981(Kedinger et al, , 1986aLouvard et al, 1992). The present study shows that LPH can be induced in Caco-2 cells in the absence of mesenchymal cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of lactase biosynthesis in the human intestinal epithelial cell line Caco‐2

Hauri

Sander

Naim

1994

European Journal of Biochemistry

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The human colonic adenocarcinoma cell line Caco-2 forms monolayers of differentiated enterocyte-like cells when cultured on permeable supports. After confluency, Caco-2 cells express a number of brush-border enzymes including lactase-phlorizin hydrolase, sucrase-isomaltase and dipeptidylpeptidase IV. We have studied, with particular emphasis on lactase-phlorizin hydrolase, the modulation of biosynthesis of these enzymes by stimulating second messenger systems. Forskolin induced lactase-phlorizin hydrolase synthesis approximately fourfold within 7 h, suppressed sucraseisomaltase synthesis, and had little effect on dipeptidylpeptidase IV. Dibutyryl-CAMP, 8-bromocAMP and vasoactive intestinal peptide also increased lactase-phlorizin hydrolase biosynthesis, indicating c-AMP dependent regulation. The induction of lactase-phlorizin hydrolase biosynthesis could be inhibited by actinomycin D and was preceded by a fourfold increase in lactase-phlorizin hydrolase mRNA levels, suggesting transcriptional control. Phorbol 12-myristate 13-acetate had an inhibitory effect on brush-border enzyme synthesis, in particular on sucrase-isomaltase, and blocked the forskolin-induced biosynthesis of lactase-phlorizin hydrolase. Lactase-phlorizin hydrolase synthesis was also inducible by hydrocortisone, but maximal induction required at least 3 days during which time sucrase-isomaltase synthesis diminished. The results indicate opposite regulation of lactase-phlorizin hydrolase and sucrase-isomaltase via cAMP and corticosteroids, and suggest that the Caco-2 cell line can serve as a model system to study aspects of the humoral regulation of human intestinal brush-border enzymes in cell culture.The human epithelial cell line Caco-2 has been established as a model system to study various aspects of intestinal epithelial cell biology including the synthesis of brushborder enzymes, protein trafficking, epithelial cell polarity (Zweibaum et al., 1991 ;Hauri and Matter, 1991 ;Louvard et al., 1992;Rodriguez-Boulan and Powell, 1992) and transepithelial transport (Thwaites et al., 1993). Although derived from a colonic adenocarcinoma, Caco-2 cells form monolayers of polarized cells on permeable supports and after confluency spontaneously express a number of features that are characteristic for differentiated small intestinal enterocytes rather than large intestinal colonocytes. As it has not been possible to establish non-transformed intestinal epithelial cell lines exhibiting a differentiated phenotype, Caco-2 remains the most promising cell line with which to study small intestinal functions in culture.Among other brush-border enzymes (Howell et al., 1992), Caco-2 cells express lactase-phlorizin hydrolase (LPH;Semenza, 1981Semenza, , 1986 Montgomery et al., 1991;Naim, 1993) which is synthesized as a 200-kDa high-man-

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“…[15][16][17][18][19] Isolated fetal endoderm may actively recruit mesenchyme interactions from recipient tissues when grafted into a host animal.20 In contrast to this abundance of evidence, there are few data to the influence of cell interactions on postnatal mucosal regeneration.…”

Section: In Vivo Grafting Studiesmentioning

confidence: 99%

Influence of cell interactions in a novel model of postnatal mucosal regeneration.

Patel

Tait²,

Evans³

et al. 1996

Gut

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Background and aims-Conventional models of postnatal mucosal regeneration are cumbersome and limited: a novel model is described here. In addition, the influence of cell interactions on mucosal regeneration is examined within the model. Methods-Postnatal rat small intestinal mucosa was digested by enzymes to yield heterotypic cell aggregates (CA). CA colony forming ability, growth, and limited cytodifferentiation were assessed in vitro. CA were transplanted subcutaneously and retrieved for histological examination at staggered intervals to assess neomucosal morphogenesis and cytodifferentiation in vivo. Cell interactions in CA were disrupted by enzymes, thus producing cell suspensions (CS). Regeneration by CA and CS were compared. Results-CA produced proliferative colonies in vitro and showed a temporal sequence of neomucosal morphogenesis and differentiation in vivo. CA colonies were more numerous within 24 hours of primary culture and had greater cellularity by 96 hours than CS colonies.Alkaline phosphatase was expressed only by 258 The continuity and absorptive function of the small intestinal mucosa is restored after inflammatory or toxic injury by mucosal regeneration. This phenomenon is a coordinated response involving constituent processes of epithelial colony formation, growth, neomucosal morphogenesis, and cytodifferentiation. Typically, surviving crypt epithelium within the injured area proliferates to form undifferentiated epithelial colonies. 14 Colonies enlarge then coalesce to restore epithelial cover.5 6 Epithelium also interacts with mesenchyme in the remodelling process of neomucosal morphogenesis to restore a three dimensional crypt/villus architecture. Epithelial cytodifferentiation provides distinct cell lineages, expressing specific enzymes and transporter proteins.7 By these processes regeneration induces a new mucosa which is indistinguishable from parent tissue.5Conventional models of mucosal regeneration involve applied injury to whole intestine in vivo, by external irradiation or systemic administration of cytotoxic drugs. 14 These methods induce mucosal damage and subsequent regeneration in vivo but are cumbersome and limited by toxicity. This study seeks to investigate methods of primary culture and grafting of disaggregated postnatal mucosa which we have previously described,78 as a model of mucosal regeneration.Factors which influence mucosal regeneration are obscure. This study has also investigated the influence of cell interactions upon the constituent processes of regeneration within the model system. Comparison ofgraft success by CA versus CS Sixteen CA grafts, 16 CS grafts, and 20 control sham operations were carried out in this assessment. All grafts were harvested at 14 days irrespective of whether a lump could be palpated. Where there was no lump, the skin and subcutaneous tissue of the graft site was harvested and examined histologically. MethodsA total of 56 CA grafts, 16 CS grafts, and 20 control sham operations were carried out.SMALL ASSESSMENT All specimens ...

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Role of epithelial-mesenchymal interactions in the ontogenesis of intestinal brush-border enzymes

Cited by 102 publications

References 25 publications

Small Intestinal Peptidases and Disaccharidases in Rats with Acute Uremia

Small Intestinal Peptidases and Disaccharidases in Rats with Acute Uremia

Induction of lactase biosynthesis in the human intestinal epithelial cell line Caco‐2

Influence of cell interactions in a novel model of postnatal mucosal regeneration.

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