Biomedical subjects

P Simon-Assmann

Publications and source records attributed to P Simon-Assmann.

At least 19 recordsLinked to original sources

PubMed1999

Developmental expression and cellular origin of the laminin alpha2, alpha4, and alpha5 chains in the intestine.

Laminins are extracellular matrix glycoproteins that are involved in various cellular functions, including adhesion, proliferation, and differentiation. In this study, we examine the expression patterns and the cellular origins of the laminin alpha2, alpha4, and alpha5 chains in the developing mouse intestine and in in vitro mouse/chick or chick/mouse interspecies hybrid intestines. In situ hybridization and Northern blot analysis revealed that mRNA levels for all three laminin alpha chains are highest in the fetal intestine undergoing intense morphogenetic movements. Laminin alpha4 mRNA and polypeptide are associated with mesenchyme-derived cell populations such as endothelium and smooth muscle. In contrast, laminin alpha2 and alpha5 chains participate in the structural organization of the subepithelial basement membrane and, in the mature intestine, show a complementary pattern of expression. All three laminin alpha chains occur in the smooth muscle basement membrane, with a differential expression of laminin alpha5 chain in the circular and longitudinal smooth muscle layers. The cellular origin of laminin alpha2 and alpha5 chains found in the subepithelial cell basement membrane was studied by immunocytochemical analysis of mouse/chick or chick/mouse interspecies hybrid intestines at various stages of development using mouse-specific antibodies. Laminin alpha2 was found to be deposited into the basement membrane exclusively by mesenchymal cells, while the laminin alpha5 chain was deposited by both epithelial and mesenchymal cells in an apparently developmentally regulated pattern. We conclude that (1) multiple laminin alpha chains are expressed in the intestine, implying specific roles for individual laminin isoforms during intestinal development, and (2) reciprocal epithelial/mesenchymal interactions are essential for the formation of a structured subepithelial basement membrane.

Animals↗

PubMed1999

Characterization of human intestinal stromal cell lines: response to cytokines and interactions with epithelial cells.

The maintenance of the physiological homeostasis of the gut mucosa characterized by continuous proliferation and differentiation processes results from epithelial-mesenchymal cell cross-talk. To set out stable and homogeneous models for the study of the (dys)regulation of various morphofunctional aspects, we established and characterized three clonal cell lines (C9, C11, and C20) derived from human duodenal mucosal connective tissue. We defined the expression of (i) cytoskeletal proteins; (ii) basement membrane molecules (laminins, collagen IV, nidogen) which have been shown formerly to be deposited at the epithelial/mesenchymal interface in situ by the mesenchymal compartment; and (iii) soluble factors, HGF, and TGFbeta1. The three cell lines display common but also specific proliferative responses to cytokines (IL1beta, IL2, IL8, TNFalpha, IFNgamma, TGFbeta1, and HGF). When cocultured with embryonic intestinal endoderms or with human colonic Caco2 or HT29 cancer cells, C9 versus C11 and C20 cell lines induced limited versus extensive growth of the associated epithelial cells. In addition C20 cells allowed spreading of HT29 cells with the formation of a basement membrane at the heterologous interface. Morphogenesis obtained by intracoelomic grafts of associations comprising the mesenchymal cell lines and intestinal endoderms was also different among those composed of C9 cells or of C11 or C20 cells. In conclusion, these data indicate that the mucosal connective tissue is heterogeneous and comprises several phenotypically different mesenchyme-derived cells whose equilibrium may be important in the gut homeostasis. These cells can now be used to define tissue-specific factors which may be involved in the physiopathology of the intestinal epithelium.

Animals↗

PubMed1998

The laminins: role in intestinal morphogenesis and differentiation.

Dynamic and reciprocal heterotypic cell interactions are crucial for intestinal morphogenesis and differentiation. This paper emphasizes the role of basement membrane molecules and in particular of laminins as potent mediators in this intercellular cross talk. Changes in the expression or localization of laminin isoforms or of integrins during development and cell migration strengthen the concept that heterogeneity in cell-matrix interactions could mediate distinct cell responses. A combination of genetic or biochemical approaches associated with in vitro models allows us to study the potential role of each laminin isoform in basement membrane assembly, cell migration, or cell differentiation.

Animals↗

PubMed1998

Human colonic cancer cells synthesize and adhere to laminin-5. Their adhesion to laminin-5 involves multiple receptors among which is integrin alpha2beta1.

In the mature gut, laminin-5 is expressed at the basal aspect of the differentiating epithelial cells. In vitro, we show that three more or less differentiated human colonic cancer HT29 cell lines produce and deposit laminin-5; they predominantly synthesize and secrete the 440 kDa form of laminin-5 that comprises the unprocessed 155 kDa gamma2 chain, as determined by immunoprecipitation analysis. In contrast, the highly differentiated colon carcinoma Caco-2 cells produce almost no laminin-5. Using anti-integrin antibodies, we show that adhesion of the two colonic cancer cell lines to laminin-5 is mediated by multiple integrin receptors including those for alpha3beta1, alpha6beta1 and alpha6beta4 integrins like in other cell types. In addition, the implication of integrin alpha2beta1 in this adhesion process is demonstrated for the first time. This has been shown by cell adhesion inhibition experiments, solid phase assays and confocal analysis. Together with previous in situ observations, these data provide a baseline knowledge for the understanding of the regulation of laminin-5 in normal and pathological intestine.

Antibodies, Monoclonal↗

PubMed1998

Cellular and molecular partners involved in gut morphogenesis and differentiation.

The intestinal mucosa represents an interesting model to study the cellular and molecular basis of epithelial-mesenchymal cross-talk participating in the development and maintenance of the digestive function. This cross-talk involves extracellular matrix molecules, cell-cell and cell-matrix adhesion molecules as well as paracrine factors and their receptors. The cellular and molecular unit is additionally regulated by hormonal, immune and neural inputs. Such integrated cell interactions are involved in pattern formation, in proximodistal regionalization, in maintenance of a gradient of epithelial proliferation and differentiation, and in epithelial cell migration. We focus predominantly on two aspects of these integrated interactions in this paper: (i) the role of basement membrane molecules, namely laminins, in the developmental and spatial epithelial behaviour; and (ii) the importance of the mesenchymal cell compartment in these processes.

Animals↗

PubMed1997

Key role of the Cdx2 homeobox gene in extracellular matrix-mediated intestinal cell differentiation.

To explore the role of homeobox genes in the intestine, the human colon adenocarcinoma cell line Caco2-TC7 has been stably transfected with plasmids synthesizing Cdx1 and Cdx2 sense and antisense RNAs. Cdx1 overexpression or inhibition by antisense RNA does not markedly modify the cell differentiation markers analyzed in this study. In contrast, Cdx2 overexpression stimulates two typical markers of enterocytic differentiation: sucrase-isomaltase and lactase. Cells in which the endogenous expression of Cdx2 is reduced by antisense RNA attach poorly to the substratum. Conversely, Cdx2 overexpression modifies the expression of molecules involved in cell-cell and cell-substratum interactions and in transduction process: indeed, E-cadherin, integrin-beta4 subunit, laminin-gamma2 chain, hemidesmosomal protein, APC, and alpha-actinin are upregulated. Interestingly, most of these molecules are preferentially expressed in vivo in the differentiated villi enterocytes rather than in crypt cells. Cdx2 overexpression also results in the stimulation of HoxA-9 mRNA expression, an homeobox gene selectively expressed in the colon. In contrast, Cdx2-overexpressing cells display a decline of Cdx1 mRNA, which is mostly found in vivo in crypt cells. When implanted in nude mice, Cdx2-overexpressing cells produce larger tumors than control cells, and form glandular and villus-like structures. Laminin-1 is known to stimulate intestinal cell differentiation in vitro. In the present study, we demonstrate that the differentiating effect of laminin-1 coatings on Caco2-TC7 cells is accompanied by an upregulation of Cdx2. To further document this observation, we analyzed a series of Caco2 clones in which the production of laminin-alpha1 chain is differentially inhibited by antisense RNA. We found a positive correlation between the level of Cdx2 expression, that of endogenous laminin-alpha1 chain mRNA and that of sucrase-isomaltase expression in these cell lines. Taken together, these results suggest (a) that Cdx1 and Cdx2 homeobox genes play distinct roles in the intestinal epithelium, (b) that Cdx2 provokes pleiotropic effects triggering cells towards the phenotype of differentiated villus enterocytes, and (c) that Cdx2 expression is modulated by basement membrane components. Hence, we conclude that Cdx2 plays a key role in the extracellular matrix-mediated intestinal cell differentiation.

Adenocarcinoma↗

PubMed1997

Cytokines modulate fibroblast phenotype and epithelial-stroma interactions in rat intestine.

BACKGROUND & AIMS: Homeostasis of the intestinal epithelium depends on interactions with the underlying connective tissue that may be altered during the pathogenesis of disease. The aim of this study was to establish whether fibroblast phenotype can influence morphogenesis and differentiation of the gut epithelium. METHODS: Permanently growing, nontumorigenic, homogenous fibroblast lines were established from postnatal rat intestinal mucosa. Their phenotypic characterization included their growth response to cytokines and expression of cytoskeletal and membrane markers, as well as expression of basement membrane components, laminin 1 and collagen IV. Their influence on epithelial growth, functional polarization, and morphogenesis was analyzed using coculture and tissue grafting of the fibroblast lines with fetal gut endoderm. RESULTS: Two intestinal fibroblast lines are described, one that supports normal intestinal morphogenesis and differentiation, and one that induces growth of fetal epithelial cells. Among the phenotypic differences between the two lines, the former differentiates into myofibroblasts in response to transforming growth factor beta1 and, in basal conditions, expresses twice as much laminin than the latter. The growth of the two lines is also affected differentially by transforming growth factor beta1 and interleukin 2. CONCLUSIONS: Cytokines, which are expressed in association with inflammation, regulate fibroblast differentiation. Fibroblasts may modify the function and organization of the overlying intestinal epithelium.

Animals↗

PubMed1996

Developmental expression of laminin-5 and HD1 in the intestine: epithelial to mesenchymal shift for the laminin gamma-2 chain subunit deposition.

We report the expression pattern of hemidesmosome-associated proteins laminin-5, composed of alpha 3 beta 3 gamma 2 chains, and HD1 in the developing mouse and human intestine, an organ in which variations in structure and function parallel morphogenesis and differentiation. Immunocytochemistry analysis revealed the coexpression of laminin-5 and HD1 at the basal pole of differentiating epithelial cells. Distinct noticeable variations occurring in the location of laminin alpha 3 chain in development of mouse gut were stressed by the reverse transcriptase-polymerase chain reaction data. A peculiar finding was also the location of laminin gamma 2 chain in the intestinal muscle coat. The cellular origin of laminin gamma 2 chain was examined by immunocytochemistry on interspecies hybrid intestines with specific antibodies recognizing mouse antigens. Complementary and sequential production of laminin gamma 2 chain was observed, by epithelial cells as establishment of the basement membrane occurs and by mesenchymal cells in the more differentiated organ. These results support the concept of mesenchymal involvement in deposition of basement membrane molecules, a crucial process for intestinal differentiation. Taken together these data provide the first evidence for the coexpression of hemidesmosome-associated proteins in the gut, a non-stratified tissue.

Aging↗

PubMed1996

Inhibition of laminin alpha 1-chain expression leads to alteration of basement membrane assembly and cell differentiation.

The expression of the constituent alpha 1 chain of laminin-1, a major component of basement membranes, is markedly regulated during development and differentiation. We have designed an antisense RNA strategy to analyze the direct involvement of the alpha 1 chain in laminin assembly, basement membrane formation, and cell differentiation. We report that the absence of alpha 1-chain expression, resulting from the stable transfection of the human colonic cancer Caco2 cells with an eukaryotic expression vector comprising a cDNA fragment of the alpha 1 chain inserted in an antisense orientation, led to (a) an incorrect secretion of the two other constituent chains of laminin-1, the beta 1/gamma 1 chains, (b) the lack of basement membrane assembly when Caco2-deficient cells were cultured on top of fibroblasts, assessed by the absence of collagen IV and nidogen deposition, and (c) changes in the structural polarity of cells accompanied by the inhibition of an apical digestive enzyme, sucrase-isomaltase. The results demonstrate that the alpha 1 chain is required for secretion of laminin-1 and for the assembly of basement membrane network. Furthermore, expression of the laminin alpha 1-chain gene may be a regulatory element in determining cell differentiation.

Base Sequence↗

PubMed1995

Extracellular matrix components in intestinal development.

Intestinal morphogenesis and differentiation are dependent on heterotypic cell interactions between embryonic epithelial cells (endoderm) and stromal cells (mesenchyme). Extracellular matrix molecules represent attractive candidates for regulators of these interactions. The structural and functional diversity of the extracellular matrix as intestinal development proceeds is demonstrated by 1) spatio-temporal specific expression of the classically described constituents, 2) the finding of laminin and collagen IV variants, 3) changes in the ratio of individual constituent chains, and 4) a stage-specific regulation of basement membrane molecule production, in particular by glucocorticoids. The orientation/assembly of these extracellular matrix molecules could direct precise cellular functions through interactions via integrin molecules. The involvement of extracellular matrix, and in particular basement membrane molecules in heterotypic cell interactions leading to epithelial cell differentiation, has been highlighted by the use of experimental models such as cocultures, hybrid intestines and antisense approaches. These models allowed us to conclude that a correct elaboration and assembly of the basement membrane, following close contacts between epithelial and fibroblastic cells, is necessary for the expression of differentiation markers such as digestive enzymes.

Animals↗

PubMed1994

Differential expression of laminin isoforms and alpha 6-beta 4 integrin subunits in the developing human and mouse intestine.

The intestinal tissue is characterized by important morphogenetic movements during development as well as by a continuous dynamic crypt to villus epithelial cell migration leading to differentiation of specialized cells. In this study, we have examined the spatio-temporal distribution of laminin A and M chains as well as of alpha 6 and beta 4 integrin subunits in adult and developing human and mouse intestine by indirect immunofluorescence. Selective expression of the constituent polypeptides of laminin isoforms (A and M chains) was demonstrated. In the mature human intestine, A and M chains were found to be complementary, the M chain being restricted to the base of crypts and the A chain lining the villus basement membrane. In the developing human intestine, M chain expression was delayed as compared to that of A chain; as soon as the M chain was visualized, it exhibited the typical localization in the crypt basement membrane. A somewhat different situation was found in the adult mouse intestine, since both M and A chains were found in the crypts. During mouse intestinal development the delayed expression of the M chain as compared to that of the A chain was also obvious. The absence of M chain expression in mutant dy mouse did not impair intestinal morphogenesis nor cell differentiation. The expression of alpha 6 and beta 4 subunits was not coordinated. In both species the alpha 6 expression preceded that of beta 4. Furthermore, while beta 4 staining in adult mouse intestine was detected at the basal surface of all cells lining the crypt-villus, that of alpha 6 was mainly confined to the crypt cell compartment. An overall similarity of location between alpha 6 integrin subunit and laminin A chain at the epithelial/stromal interface was noted. These data indicate that the spatial and temporal distribution of laminin variants in the developing intestine may be characteristic for each species and that interactions of laminin variants with particular receptors may be important for induction and/or maintenance of differentiated cells.

Adult↗

PubMed1994

Adhesive properties and integrin expression profiles of two colonic cancer populations differing by their spreading on laminin.

The mostly undifferentiated parental HT29 (HT29p) human colonic adenocarcinoma cell line and a differentiated subpopulation selected by the anti-cancer drug 5-fluorouracil (HT29-Fu) (Lesuffleur et al. (1991) Int. J. Cancer 49, 721-730) display strikingly different behavior when grown on laminin coatings: the former grows as aggregates while the latter grows as monolayers. In an attempt to explain this difference, we performed a comparative study of cell adhesion properties and of expression, involvement and localization of the alpha 6, beta 1 and beta 4 subunits constituting the integrin family among the two cell populations. HT29p and HT29-Fu cells exhibited a similar adhesion pattern to laminin and laminin fragments E8 and P1. In both cell lines, cell adhesion could be blocked at about 90% with anti-alpha 6 subunit antibodies and around 30-50% with anti-beta 1 antibodies; no inhibition of the cell adhesion was obvious when using anti-beta 4 antibodies. Immunoprecipitations of iodinated membrane-solubilized proteins and immunoblotting experiments showed that all alpha 6 chains expressed in both HT29p and HT29-Fu cell populations exist as alpha 6 beta 4 integrins; beta 1 subunits are associated with alpha 2 and alpha 3 chains. When HT29p or HT29-Fu cells were injected subcutaneously in nude mice, a similar expression pattern of alpha 6, beta 4 and beta 1 integrin subunits was noticeable in the resulting tumors: alpha 6 and beta 4 subunits were localized at the basal surface of the tumor cells facing the stromal elements, and to a lesser extent at the cell-cell contacts within the tumor-cell clumps; beta 1 subunits were mainly found within the cytoplasm of the tumor cells. Despite these overall similarities among the two cell lines, the following changes could account for their different behavior on laminin: less proteolytic processing of the beta 4 integrin subunit occurred in HT29-Fu cells yielding peptidic fragments of 175 kDa, which are absent from the parental cells; the immunostaining pattern of the various subunits demonstrated a segregation of alpha 6, beta 4 and beta 1 integrin subunits on the basal side of the HT29-Fu cells when cultured on laminin to the detriment of their lateral location, a phenomenon that was not obvious in the parental cells. Altogether, these results suggest that the distinct behavior of the undifferentiated versus differentiated HT29 cell populations on laminin is not related to altered adhesion properties of the cells but rather to a deficient stabilization of the adhesion leading to cell spreading.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

[Expression of laminin is correlated to the differentiation of human colonic cancer cells].

The level and molecular composition of laminin, a major basement membrane glycoprotein formed of three chains (A, B1 and B2) have been analyzed in various human colonic cancer cells (Caco-2 and HT29). The synthesis of laminin over a 24 h period, corresponding to cellular and secreted molecules purified by affinity chromatography, was the highest in the more differentiated cells. Immunocytochemical detection of the constituent chains of laminin in permeabilized cells as well as after separation on polyacrylamide gels showed that A, B1 and B2 chains were expressed in Caco-2 cells, whereas A chain was not detected in HT29 cells. When cancer cells were cultured on a monolayer of confluent fibroblastic cells, laminin was deposited at the basement membrane level only in the case of the most differentiated cells. In an attempt to define the role of laminin-A chain, transfection of Caco-2 cells with A chain antisense cDNA was performed; among the clones obtained, 3 were deficient for the target polypeptide. The consequences of the absence of laminin-A chain on basement membrane formation, cellular differentiation and tumor invasion will be currently determined.

Basement Membrane↗

PubMed1993

Heterotypic cellular cooperation in gut morphogenesis and differentiation.

The development of the gastrointestinal tract, like that of other organs, results from the association of intrinsic genetic endowment, endogenous regulatory mechanisms and environmental influences. The present chapter emphasizes the role of epithelial-mesenchymal interactions during development and crypt-villus migration. Arguments are given as to the role of basement membrane molecules as mediators for these cell interactions. Differential developmental expression of the various extracellular matrix components, which precedes the onset of differentiation markers, suggests that each of these molecules assumes a specific task. Yet, much work still remains to be done before knowing exactly how transfer of morphogenetic signals between epithelial and mesenchymal tissues occurs.

Animals↗

PubMed1992

Dual and asynchronous deposition of laminin chains at the epithelial-mesenchymal interface in the gut.

The production of laminin by 14-day fetal rat intestinal endoderm and mesenchyme was investigated. The amount of neosynthesized laminin was measured after purification using affinity chromatography. Chain composition of laminin was analyzed by immunoblotting and immunofluorescence staining. The data show that both embryonic intestinal tissue components synthesize laminin and that A and B1/B2 chains were detected in both endodermal and mesenchymal cells. The cellular source of laminin found at the epithelial basement membrane has been studied by immunocytochemistry in rat/chick or mouse/chick interspecies hybrid intestines taken at various stages of development. Immunodetection of the whole laminin molecule and of the individual A and B1/B2 chains by rodent-specific polyclonal and monoclonal antibodies at the basement membrane level in these hybrid intestines revealed (a) laminin molecules, which originate from both mesenchymal and endodermal cells; (b) deposition of A and B1/B2 chains by endodermal cells, regardless of the stage of growth of the hybrid intestines; and (c) asynchronous deposition of the various chains of laminin into the basement membrane by the mesenchyme. B1/B2 chains are deposited concomitant with contact with the epithelium, whereas A chains appear only later (13 days after grafting). These data reinforce the suggestion from previous studies that cooperation between epithelium and mesenchyme is necessary for the formation of a complete basement membrane in the developing intestine.

Animals↗

PubMed1992

Mesenchyme-mediated effect of dexamethasone on laminin in cocultures of embryonic gut epithelial cells and mesenchyme-derived cells.

Previous studies have shown that glucocorticoids accelerate intestinal maturation and that this process is mediated by the mesenchymal cells. The possible involvement of laminin (LN), a basement membrane component, in this mesenchymal mediation has been analyzed. For this purpose, the influence of dexamethasone (DX) on the synthesis of LN, its chain composition and its cellular distribution has been examined biochemically and immunocytochemically in two different mesenchyme-derived cell populations, fetal intestinal mesenchymal cells and fetal skin fibroblasts, as well as in cocultures of intestinal endodermal cells seeded on top of confluent fetal skin fibroblasts. Neither the amount of metabolically labeled LN purified by affinity chromatography (expressed per mg cell proteins), nor the A versus B chain ratio monitored after separation on gel electrophoresis and immunoblotting, showed significant differences after 5 days of DX treatment. However, glucocorticoids induced a shift from secreted to cell-associated LN molecules paralleling a striking difference in the immunostaining pattern of intracellular and surface LN in the mesenchyme-derived cell monocultures; the granular intracytoplasmic LN staining in the control cultures was replaced by a fibrillar organization of LN molecules concomitantly with an increased accumulation at the cell surface. In 2-day DX-treated cocultures, there was an acceleration of LN deposition at the epithelial-fibroblastic interface, which accompanied the enhanced expression of epithelial cell differentiation markers (brush border digestive enzymes). These DX-induced changes can be blocked by the addition of anti-LN antibodies in the culture medium. These findings further support the concept that glucocorticoid action on intestinal epithelial cells involves alterations in the extracellular microenvironment, assessed here for LN molecules, occurring at the level of the mesenchymal cell compartment. These changes may contribute to an accelerated organization of LN at the epithelial-mesenchymal interface and subsequently to epithelial differentiation.

Animals↗

PubMed1991

Altered deposition of basement-membrane molecules in co-cultures of colonic cancer cells and fibroblasts.

Two human colon carcinoma cell lines, HT29 and Caco-2 were co-cultured with fetal rat or human skin fibroblasts. Their morphological features, ultra-structural characteristics at the heterologous cell interface, and the deposition of basement-membrane molecules [laminin, type-IV collagen, heparan sulfate proteoglycan (HSPG)] at the epithelial-stromal junction were analyzed. The 2 cell lines behaved differently. HT29 cells did not spread on the fibroblasts and grew as clusters, while Caco-2 cells formed a monolayer over the fibroblastic feeder layer. Only the latter carcinoma cells exhibited cytoplasmic processes towards the fibroblasts and, after 5 days in co-cultures, a structured basement membrane (BM). The immunocytochemical analysis of the BM constituents revealed the absence of the molecules studied at the sites of heterologous contacts in the case of HT29 cells. In contrast, in the co-cultures comprising Caco-2 cells, laminin and type-IV collagen were progressively deposited in a polar fashion at the epithelial-fibroblastic interface which, however, remained devoid of HSPG molecules. Together with earlier data indicating a dual origin of the BM molecules located at the epithelial-fibroblastic interface in normal intestine, the present study shows that the cancer cells as well as the fibroblastic ones under the influence of carcinoma cells display an altered capacity to synthesize and/or secrete BM molecules. The extent of such abnormalities correlates with the differentiation of the cells. Finally, these modifications occur concomitantly with alterations in cell interactions which vary among cell lines.

Adenocarcinoma↗

PubMed1991

Changes in glycosaminoglycan expression in the rat developing intestine.

Synthesis of glycosaminoglycan (GAG) chains was studied in the developing rat intestine. Intestinal segments, taken at various developmental stages, were exposed to 3H-glucosamine and 35S-sulfate for 6 hours. The amounts of 3H-GAGs (total GAGs) and of 35S-GAGs (sulfated GAGs) showed a clear age-dependence, with a broad maximum in the fetal period when dramatic growth and morphogenesis occur. Characterization of individual GAG species indicated that hyaluronic acid (HA), heparan and chondroitin sulfate (HS and CS) synthesis was modified quantitatively or qualitatively during development: decrease of HA with age; production of undersulfated HS molecules during embryonic life; shift towards a lower hydrodynamic form of HA and HS molecules after birth. We postulate that these alterations are crucial in the elaboration of an age-related specific extracellular microenvironment allowing intestinal growth and differentiation.

Aging↗