scholarly journals Fibroblast growth factor 10 alters the balance between goblet and Paneth cells in the adult mouse small intestine

2015 ◽  
Vol 308 (8) ◽  
pp. G678-G690 ◽  
Author(s):  
Denise Al Alam ◽  
Soula Danopoulos ◽  
Kathy Schall ◽  
Frederic G. Sala ◽  
Dana Almohazey ◽  
...  
Keyword(s):  
Small Intestine ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Paneth Cells ◽  
Intestinal Epithelial ◽  
Mouse Small Intestine ◽  
Fibroblast Growth Factor 10 ◽  
Goblet Cell Differentiation

Intestinal epithelial cell renewal relies on the right balance of epithelial cell migration, proliferation, differentiation, and apoptosis. Intestinal epithelial cells consist of absorptive and secretory lineage. The latter is comprised of goblet, Paneth, and enteroendocrine cells. Fibroblast growth factor 10 (FGF10) plays a central role in epithelial cell proliferation, survival, and differentiation in several organs. The expression pattern of FGF10 and its receptors in both human and mouse intestine and their role in small intestine have yet to be investigated. First, we analyzed the expression of FGF10, FGFR1, and FGFR2, in the human ileum and throughout the adult mouse small intestine. We found that FGF10, FGFR1b, and FGFR2b are expressed in the human ileum as well as in the mouse small intestine. We then used transgenic mouse models to overexpress Fgf10 and a soluble form of Fgfr2b, to study the impact of gain or loss of Fgf signaling in the adult small intestine. We demonstrated that overexpression of Fgf10 in vivo and in vitro induces goblet cell differentiation while decreasing Paneth cells. Moreover, FGF10 decreases stem cell markers such as Lgr5, Lrig1, Hopx, Ascl2, and Sox9. FGF10 inhibited Hes1 expression in vitro, suggesting that FGF10 induces goblet cell differentiation likely through the inhibition of Notch signaling. Interestingly, Fgf10 overexpression for 3 days in vivo and in vitro increased the number of Mmp7/Muc2 double-positive cells, suggesting that goblet cells replace Paneth cells. Further studies are needed to determine the mechanism by which Fgf10 alters cell differentiation in the small intestine.

scholarly journals Bacteria Regulate Intestinal Epithelial Cell Differentiation Factors Both In Vitro and In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55620 ◽  
Author(s):  
Svetlana Becker ◽  
Tobias A. Oelschlaeger ◽  
Andy Wullaert ◽  
Manolis Pasparakis ◽  
Jan Wehkamp ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Differentiation ◽  
Differentiation Factors

Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study

BioMetals ◽  
2014 ◽  
Vol 27 (5) ◽  
pp. 857-874 ◽  
Author(s):  
Anne Blais ◽  
Cuibai Fan ◽  
Thierry Voisin ◽  
Najat Aattouri ◽  
Michel Dubarry ◽  
...  
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
In Vitro Study ◽  
Vitro Study ◽  
Intestinal Epithelial ◽  
Cell Growth And Differentiation

scholarly journals Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

2020 ◽  
Vol 295 (13) ◽  
pp. 4237-4251 ◽  
Author(s):  
Jie Zhang ◽  
Min Xu ◽  
Weihua Zhou ◽  
Dejian Li ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Epithelial Cell ◽  
Bowel Disease ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
P53 Expression ◽  
Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

Localized distribution of alpha 9 integrin in the cornea and changes in expression during corneal epithelial cell differentiation.

1995 ◽  
Vol 43 (4) ◽  
pp. 353-362 ◽  
Author(s):  
M A Stepp ◽  
L Zhu ◽  
D Sheppard ◽  
R L Cranfill
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Corneal Epithelium ◽  
Corneal Epithelial Cell ◽  
Basal Cells ◽  
Postnatal Maturation ◽  
Central Cornea ◽  
Epithelial Cell Differentiation

A recently characterized integrin alpha-chain, alpha 9, forms heterodimers with the integrin beta 1-chain and is present in the skin with a distribution similar to that of alpha 2 and alpha 3, other beta 1 integrins. To determine whether alpha 9 is expressed in the stratified squamous epithelium of the cornea, we used immunohistochemical techniques to compare the distribution of alpha 9 in the adult mouse cornea with that of alpha 3. Abundant alpha 9 was expressed in the lateral and basal membranes of the basal cells of the conjunctiva and corneal limbus, but very little alpha 9 was present in the basal cells of the central corneal epithelium. In contrast, alpha 3 was present in the membranes of basal cells of the conjunctiva, limbus, and central cornea. To determine when during postnatal maturation of the corneal epithelium alpha 9 becomes restricted to the limbus, we looked at the distribution of alpha 9 and alpha 3 in the developing mouse eye from birth to eyelid opening. At birth, the basal cells of the cornea and developing limbal region did not express alpha 9, but there was abundant alpha 9 expressed in suprabasal cells between the fused lids and in the basal cells of the skin and conjunctiva. In contrast, alpha 3, integrin was expressed uniformly in the basal cells across the surface of the conjunctiva, limbus, and cornea and was present only in the basal cells of the epithelium between the fused eyelids. In the central cornea, alpha 9 expression increased in basal cells up until Day 10 after birth. After Day 10, alpha 9 expression in the central cornea began to decrease; after the lids were open, alpha 9 expression in the central cornea became restricted to the limbus. In the basal and suprabasal cells between the fused eyelids expression of alpha 9 became increasingly restricted over time to the basal cells. Recent data suggest that alpha 9 beta 1 can interact with tenascin. Our dual labeling confocal microscopy studies indicate that localization of alpha 9 and tenascin are not coordinated in the developing mouse cornea. Many recent studies have shown an important role for beta 1 integrins in mediating epithelial cell differentiation in vitro; in vivo, changes in integrin expression have been found in wound healing, psoriasis, and in basal and squamous cell carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

The influence of protein fractions from bovine colostrum digested in vivo and in vitro on human intestinal epithelial cell proliferation

2014 ◽  
Vol 81 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Alison J Morgan ◽  
Lisa G Riley ◽  
Paul A Sheehy ◽  
Peter C Wynn
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Proliferative Activity ◽  
Intestinal Epithelial Cell ◽  
Bovine Colostrum ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Human Intestinal Epithelial Cell

Colostrum consists of a number of biologically active proteins and peptides that influence physiological function and development of a neonate. The present study investigated the biological activity of peptides released from first day bovine colostrum through in vitro and in vivo enzymatic digestion. This was assessed for proliferative activity using a human intestinal epithelial cell line, T84. Digestion of the protein fraction of bovine colostrum in vitro was conducted with the enzymes pepsin, chymosin and trypsin. Pepsin and chymosin digests yielded protein fractions with proliferative activity similar to that observed with undigested colostrum and the positive control foetal calf serum (FCS). In contrast trypsin digestion significantly (P<0·05) decreased colostral proliferative activity when co-cultured with cells when compared with undigested colostrum. The proliferative activity of undigested colostrum protein and abomasal whey protein digesta significantly increased (P<0·05) epithelial cell proliferation in comparison to a synthetic peptide mix. Bovine colostrum protein digested in vivo was collected from different regions of the gastrointestinal tract (GIT) in newborn calves fed either once (n=3 calves) or three times at 12-h intervals (n=3 calves). Digesta collected from the distal duodenum, jejunum and colon of calves fed once, significantly (P<0·05) stimulated cell proliferation in comparison with comparable samples collected from calves fed multiple times. These peptide enriched fractions are likely to yield candidate peptides with potential application for gastrointestinal repair in mammalian species.

scholarly journals DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine

2004 ◽  
Vol 379 (3) ◽  
pp. 687-695 ◽  
Author(s):  
Fumio OMAE ◽  
Masao MIYAZAKI ◽  
Ayako ENOMOTO ◽  
Minoru SUZUKI ◽  
Yusuke SUZUKI ◽  
...  
Keyword(s):  
Small Intestine ◽  
Epithelial Cells ◽  
Intestinal Epithelial ◽  
Vitro Assay ◽  
Peptide Antibody ◽  
Mouse Small Intestine ◽  
Mrna Content ◽  
Crypt Cells

The C-4 hydroxylation of sphinganine and dihydroceramide is a rate-limiting reaction in the biosynthesis of phytosphingolipids. Mouse DES1 (MDES1) cDNA homologous to the Drosophila melanogaster degenerative spermatocyte gene-1 (des-1) cDNA leads to sphingosine Δ4-desaturase activity, and another mouse homologue, MDES2, has bifunctional activity, producing C-4 hydroxysphinganine and Δ4-sphingenine in yeast [Ternes, Franke, Zahringer, Sperling and Heinz (2002) J. Biol. Chem. 277, 25512–25518]. Here, we report the characterization of mouse DES2 (MDES2) using an in vitro assay with a homogenate of COS-7 cells transfected with MDES2 cDNA and N-octanoyl-sphinganine and sphinganine as substrates. MDES2 protein prefers dihydroceramide as a substrate to sphinganine, and exhibits dihydroceramide Δ4-desaturase and C-4 hydroxylase activities. MDES2 mRNA content was high in the small intestine and abundant in the kidney. In situ hybridization detected signals of MDES2 mRNA in the crypt cells. Immunohistochemistry using an anti-MDES2 peptide antibody stained the crypt cells and the adjacent epithelial cells. These results suggest that MDES2 is the dihydroceramide C-4 hydroxylase responsible for the biosynthesis of enriched phytosphingoglycolipids in the microvillous membranes of intestinal epithelial cells.

scholarly journals Rapid protein kinase D1 signaling promotes migration of intestinal epithelial cells

2012 ◽  
Vol 303 (3) ◽  
pp. G356-G366 ◽  
Author(s):  
Steven H. Young ◽  
Nora Rozengurt ◽  
James Sinnett-Smith ◽  
Enrique Rozengurt
Keyword(s):  
Protein Kinase ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Transgenic Mice ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Protein Kinase D1

We have examined the role of protein kinase D1 (PKD1) signaling in intestinal epithelial cell migration. Wounding monolayer cultures of intestinal epithelial cell line IEC-18 or IEC-6 induced rapid PKD1 activation in the cells immediately adjacent to the wound edge, as judged by immunofluorescence microscopy with an antibody that detects the phosphorylated state of PKD1 at Ser916, an autophosphorylation site. An increase in PKD1 phosphorylation at Ser916 was evident as early as 45 s after wounding, reached a maximum after 3 min, and persisted for ≥15 min. PKD1 autophosphorylation at Ser916 was prevented by the PKD family inhibitors kb NB 142-70 and CRT0066101. A kb NB 142-70-sensitive increase in PKD autophosphorylation was also elicited by wounding IEC-6 cells. Using in vitro kinase assays after PKD1 immunoprecipitation, we corroborated that wounding IEC-18 cells induced rapid PKD1 catalytic activation. Further results indicate that PKD1 signaling is required to promote migration of intestinal epithelial cells into the denuded area of the wound. Specifically, treatment with kb NB 142-70 or small interfering RNAs targeting PKD1 markedly reduced wound-induced migration in IEC-18 cells. To test whether PKD1 promotes migration of intestinal epithelial cells in vivo, we used transgenic mice that express elevated PKD1 protein in the small intestinal epithelium. Enterocyte migration was markedly increased in the PKD1 transgenic mice. These results demonstrate that PKD1 activation is one of the early events initiated by wounding a monolayer of intestinal epithelial cells and indicate that PKD1 signaling promotes the migration of these cells in vitro and in vivo.

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