The repair of superficially damaged intestinal epithelium is initiated by restitution. Restitution is the covering of damaged area by the movement of neighboring epithelial cells without cell proliferation. Phenotypic switching of cells (epithelial-mesenchymal transition) is necessary for the cell movement and this process is controlled by complex intracellular signaling pathways conducting dynamic remodeling of actin cytoskeleton. Restitution is regulated by a variety of cytokines and growth factors, and is modulated by integrin-dependent interactions with the extracellular matrix. Understanding the restitution process suggests several possible therapeutic strategies to enhance gastrointestinal wound healing.
Cell Movement ; Humans ; Intestinal Mucosa/*physiology ; Regeneration/*physiology

The repair of superficially damaged intestinal epithelium is initiated by restitution. Restitution is the covering of damaged area by the movement of neighboring epithelial cells without cell proliferation. Phenotypic switching of cells (epithelial-mesenchymal transition) is necessary for the cell movement and this process is controlled by complex intracellular signaling pathways conducting dynamic remodeling of actin cytoskeleton. Restitution is regulated by a variety of cytokines and growth factors, and is modulated by integrin-dependent interactions with the extracellular matrix. Understanding the restitution process suggests several possible therapeutic strategies to enhance gastrointestinal wound healing.
Cell Movement ; Humans ; Intestinal Mucosa/*physiology ; Regeneration/*physiology

No abstract available.
Animals ; Apoptosis/*physiology ; Claudins/*metabolism ; Colitis/*physiopathology ; Intestinal Mucosa/*physiopathology ; Mannose-Binding Lectin/*immunology

This study was aimed to evaluate the cellular compatibility of the small intestinal submucosal(e) (SIS). Prepared by use of pig jejunum. SIS were cocultured with human embryonic periosteal osteoblasts (HEPOB), human embryonic skin fibroblasts (HESFB) and rabbit renal vascular endothelial cells (RRVEC) respectively. The cell growth, attachment, cell cycle, cell apoptosis rate were detected to evaluate the cellular compatibility of SIS. The three kinds of cells attached onto SIS and grew well. SIS accelerated the growth of RRVEC. No effects of SIS were detected on cell cycle and cell apoptosis rate in the three kinds of cells. SIS has good cellular compatibility without cytotoxicity. The porous structure of SIS is suited for the growth of HEPOB, HESFB and RRVEC in three dimensions in the scaffold. SIS is a good bio-derived material of tissue engineering.
Animals ; Cell Differentiation ; physiology ; Cell Division ; physiology ; Cells, Cultured ; Coculture Techniques ; Extracellular Matrix ; physiology ; Histocompatibility ; Intestinal Mucosa ; cytology ; Jejunum ; cytology ; Osteoblasts ; cytology ; physiology ; Swine ; Tissue Engineering

Animals ; Gene Expression Regulation ; physiology ; Gills ; metabolism ; Intestinal Mucosa ; metabolism ; Lancelets ; genetics ; metabolism ; Liver ; metabolism ; MicroRNAs ; biosynthesis ; genetics

Bacterial Translocation ; physiology ; Humans ; Intestinal Mucosa ; pathology ; physiology ; Lipopolysaccharides ; metabolism ; physiology ; Liver Failure, Acute ; etiology ; immunology ; physiopathology ; Lymphocytes ; immunology ; metabolism ; Macrophages ; immunology ; metabolism ; Signal Transduction ; genetics ; physiology ; Toll-Like Receptor 4 ; metabolism ; physiology

Epithelial cells line the gastrointestinal (GI) mucosa and form an important barrier that protects the subepithelial tissue against a wide array of noxious substances, allergens, viruses, and luminal microbial pathogens. Restoration of mucosal integrity following injury requires epithelial cell decisions that regulate signaling networks controlling gene expression, survival, migration, and proliferation. Over the past few years, polyamines have been shown to play a critical role in GI mucosal repair, and the control of cellular polyamines is a central convergence point for the multiple signaling pathways. Both the function of polyamines in rapid intestinal mucosal epithelial restitution and the underlying mechanism, especially the implication of K(+) channel activity, are the subject of this mini-review article.
Animals ; Cell Movement ; Epithelial Cells ; metabolism ; pathology ; physiology ; Gene Expression Regulation ; Humans ; Intestinal Mucosa ; cytology ; pathology ; physiology ; Membrane Potentials ; Polyamines ; metabolism ; Potassium Channels ; physiology ; Signal Transduction ; Wound Healing ; physiology

OBJECTIVETo investigate the role of integrin α4β7 in the development of ulcerative colitis (UC) in rats.

METHODSSixty Sprague-Dawley rats were randomly divided into the control group (acetone enema), the model group (2,4-dinitrochlorobenzene, DNCB enema), and the α4 intervention group. Colonic mucosa of different groups was observed and compared in terms of pathology and cytokine changes(IL-2 and IL-6) using ELISA. Semi-quantitative RT-PCR was used to detect the colon α4β7 expression. Integrin α4β7(+) lymphocytes in the portal vein of rats were determined by flow cytometry.

RESULTSThe expression of α4 mRNA was 0.68±0.24 in the model group and 0.58±0.37 in the intervention group, and the expression of β7 mRNA was 0.84±0.37 in the model group and 0.65±0.30 in the intervention group, which were all significantly higher as compared to those in the control group(0.15±0.13 for α4 and 0.24±0.62 for β7, P<0.01). The proportions of integrin α4β7 positive lymphocytes in the portal vein in the model group and intervention group were significantly higher than that in the control group [(76.7±8.2)% and (68.2±7.6)% vs. (14.7±6.7)%, P<0.01]. The expression of IL-2 and IL-6 and the result of macroscopic and microscopic scores in the intervention group were lower than those in the model group(P<0.05).

CONCLUSIONSHigh expression of α4β7 may play an important role in experimental colon mucosa inflammation in rats with ulcerative colitis. The blockade of integrin α4β7 may be a potential target to reduce colonic mucosa inflammation.

Animals ; Colitis, Ulcerative ; metabolism ; pathology ; Colon ; metabolism ; pathology ; Disease Models, Animal ; Female ; Integrins ; metabolism ; physiology ; Interleukin-2 ; metabolism ; Interleukin-6 ; metabolism ; Intestinal Mucosa ; pathology ; Rats

OBJECTIVETo investigate the effect of mesenteric lymph drainage on intestinal barrier function in severe intraperitoneal infection (SII).

METHODSThirty healthy male Wistar rats were randomly divided into 3 groups(model group, drainage group and control group). SII model rats were prepared by injecting E.coli intraperitoneally. Rats in drainage group rats underwent mesentery lymphatic duct ligation and drainage 2 hours after model induction, and those in control group received equal amount of 10% BaSO4 nutrient broth injection intraperitonerally. Six hours after model induction, rats were sacrificed. The intestinal samples were collected for pathology analysis and content of DAO and concentration of TNF-α, IL-6. Content of D-lactate in blood plasma was detected.

RESULTSUnder light microscopy, ileum mucosa tissue structure of model group was disordered. Under transmission electron microscopy, intestinal mucosal epithelial cells of model group swelled obviously, close connection was destructed, and early apoptosis cells occurred. After mesentery lymph drainage, intestinal mucosa tissue structure was improved obviously, endoplasmic reticulum and mitochondria of epithelium swelled mildly. The contents of intestinal tissue DAO in drainage group, model group and control group were (5.9±0.4) U/L, (3.0±0.1) U/L and (18.3±2.1) U/L respectively. There was significant difference among groups (P<0.05). Compared with control group [(45.4±37.9) μg/L], the plasma content of D-lactate in model group [(256.0±177.2) μg/L] increased significantly (P<0.05). The plasma content of D-lactate in drainage group [(136.9±21.5) μg/L] was not significantly different compared with model group (P>0.05), but was significantly higher compared to control group (P<0.05). Compared with control group, model group had significantly higher levels of TNF-α [(3431.3±23.9) ng/L vs. (2730.0±408.7) ng/L] and IL-6 [(86.3±1.6) ng/L vs. (30.2±0.9) ng/L] (P<0.05), while the TNF-α was (2653.2±324.1) ng/L, and the IL-6 was (50.9±0.7) ng/L in drainage group, which were significantly lower compared with model group (P<0.05).

CONCLUSIONMesenteric lymph drainage can obviously improve intestinal barrier function in severe intraperitoneal infection and may play a protective role in intestinal mucosa.

Animals ; Drainage ; Interleukin-6 ; Intestinal Mucosa ; physiology ; Lymph Nodes ; Male ; Mesentery ; Peritoneal Diseases ; therapy ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha

Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed additive effect with FSK and 3-Isobutyl-1-methylx (IBMX) in the activation of CFTR, while had no additive effect with genistein (GEN). In ex vivo studies, HMF and HTF could stimulate transepithelial Cl(-) secretion in rat colonic mucosa and enhance fluid secretion in mouse trachea submucosal glands. These results suggest that HMF and HTF may potentiate CFTR Cl(-) channel activities through both elevation of cAMP level and binding to CFTR protein pathways. The results provide new clues in elucidating structure and activity relationship of flavonoid CFTR activators. HMF might be developed as a new drug in the therapy of CFTR-related diseases such as bronchiectasis and habitual constipation.
Animals ; Colforsin ; Colon ; metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator ; drug effects ; Flavones ; physiology ; Flavonoids ; pharmacology ; Genistein ; Intestinal Mucosa ; metabolism ; Mice ; Rats