maintenance of gastrointestinal epithelium
Definition
Target type: biologicalprocess
Protection of epithelial surfaces of the gastrointestinal tract from proteolytic and caustic digestive agents. [GOC:mah]
The maintenance of the gastrointestinal (GI) epithelium is a complex and tightly regulated process that involves a delicate balance of cell proliferation, differentiation, and apoptosis. This dynamic process ensures the constant renewal of the GI lining, which is exposed to a harsh environment containing digestive enzymes, acids, and microbes.
**1. Cell Proliferation:**
* The GI epithelium is constantly renewed from specialized stem cells located in specific niches within the crypts of the small intestine and the base of the gastric glands. These stem cells undergo rapid and continuous proliferation, giving rise to a pool of progenitor cells.
* The rate of cell proliferation in the GI tract is influenced by various factors, including dietary components, hormones, and growth factors. For example, Wnt signaling plays a crucial role in promoting stem cell proliferation and maintaining the stem cell pool.
**2. Cell Differentiation:**
* As progenitor cells migrate upward towards the luminal surface of the GI tract, they undergo progressive differentiation into specialized epithelial cells.
* Different regions of the GI tract contain distinct cell types, each adapted to its specific function. For example, the small intestine contains enterocytes for nutrient absorption, goblet cells for mucus production, Paneth cells for antimicrobial peptide secretion, and enteroendocrine cells for hormone secretion.
* The differentiation process is governed by complex regulatory networks involving transcription factors, signaling pathways, and epigenetic modifications.
**3. Cell Apoptosis:**
* As epithelial cells reach the apical surface of the GI tract, they undergo programmed cell death or apoptosis. This controlled process ensures the removal of old or damaged cells, maintaining the integrity and functionality of the epithelium.
* Apoptosis is triggered by various mechanisms, including intrinsic pathways (e.g., p53-mediated stress response) and extrinsic pathways (e.g., death receptor activation).
**4. Factors Influencing Maintenance:**
* **Dietary factors:** Nutrients, fiber, and probiotics play crucial roles in maintaining the health and function of the GI epithelium. For example, a balanced diet rich in fiber promotes the growth of beneficial bacteria in the gut, which contribute to epithelial barrier function and immune system regulation.
* **Immune system:** The GI tract is constantly exposed to a vast array of antigens, and the immune system plays a critical role in maintaining epithelial homeostasis. Immune cells, such as T cells and macrophages, reside within the epithelium and contribute to pathogen clearance and tissue repair.
* **Hormones and growth factors:** Several hormones and growth factors influence epithelial cell proliferation, differentiation, and apoptosis. For example, epidermal growth factor (EGF) and transforming growth factor-beta (TGF-β) are involved in wound healing and epithelial repair.
**5. Disruptions in Epithelial Maintenance:**
* Disruptions in the delicate balance of cell proliferation, differentiation, and apoptosis can lead to a variety of pathological conditions, including inflammatory bowel disease (IBD), colorectal cancer, and infections.
* Factors such as genetic predisposition, environmental factors, and lifestyle choices can contribute to disruptions in epithelial maintenance.
In summary, the maintenance of the gastrointestinal epithelium is a dynamic and intricate process that ensures the constant renewal and integrity of the GI lining. It involves a complex interplay of cell proliferation, differentiation, and apoptosis, which are influenced by various factors, including dietary components, immune system function, and hormones. Proper epithelial maintenance is essential for maintaining the health and functionality of the GI tract, while disruptions in this process can lead to a variety of diseases.'
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Proteins (4)
| Protein | Definition | Taxonomy |
|---|---|---|
| Toll-like receptor 9 | A Toll-like receptor 9 that is encoded in the genome of human. [] | Homo sapiens (human) |
| Nucleotide-binding oligomerization domain-containing protein 2 | A nucleotide-binding oligomerization domain-containing protein 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9HC29] | Homo sapiens (human) |
| 5-hydroxytryptamine receptor 4 | A 5-hydroxytryptamine receptor 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q13639] | Homo sapiens (human) |
| Retinol-binding protein 4 | A retinol-binding protein 4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P02753] | Homo sapiens (human) |
Compounds (53)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| methylbufotenin | 5-methoxy-N,N-dimethyltryptamine : A tryptamine alkaloid that is N,N-dimethyltryptamine substituted by a methoxy group at position 5. | aromatic ether; tertiary amino compound; tryptamine alkaloid | hallucinogen; plant metabolite |
| 5-methoxytryptamine | 5-methoxytryptamine : A member of the class of tryptamines that is the methyl ether derivative of serotonin. 5-Methoxytryptamine: Serotonin derivative proposed as potentiator for hypnotics and sedatives. | aromatic ether; primary amino compound; tryptamines | 5-hydroxytryptamine 2A receptor agonist; 5-hydroxytryptamine 2B receptor agonist; 5-hydroxytryptamine 2C receptor agonist; antioxidant; cardioprotective agent; human metabolite; mouse metabolite; neuroprotective agent; radiation protective agent; serotonergic agonist |
| cisapride | cisapride : The amide resulting from formal condensation of 4-amino-5-chloro-2-methoxybenzoic acid with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-amine. It has been used (as its monohydrate or as its tartrate) for the treatment of gastro-oesophageal reflux disease and for non-ulcer dyspepsia, but its propensity to cause cardiac arrhythmias resulted in its complete withdrawal from many countries, including the U.K., and restrictions on its use elsewhere. Cisapride: A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed) | benzamides | |
| ebastine | organic molecular entity | ||
| haloperidol | haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| hydroxychloroquine | hydroxychloroquine : An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions. Hydroxychloroquine: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970) | aminoquinoline; organochlorine compound; primary alcohol; secondary amino compound; tertiary amino compound | anticoronaviral agent; antimalarial; antirheumatic drug; dermatologic drug |
| sdz 205-557 | methoxybenzoic acid | ||
| metergoline | metergoline : An ergoline alkaloid that is the N-benzyloxycarbonyl derivative of lysergamine. A 5-HT2 antagonist. Also 5-HT1 antagonist and 5-HT1D ligand. Has moderate affinity for 5-HT6 and high affinity for 5-HT7. Metergoline: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy. | carbamate ester; ergoline alkaloid | dopamine agonist; geroprotector; serotonergic antagonist |
| paclitaxel | Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL). | taxane diterpenoid; tetracyclic diterpenoid | antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent |
| gr 127935 | GR 127935 : A member of the class of benzamides obtained by formal condensation of the carboxy group of 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid and the anilino group of 4-methoxy-3-(4-methylpiperazin-1-yl)aniline. Potent and selective 5-HT1B/1D receptor antagonist (pKi values are 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptors). Displays > 100-fold selectivity over 5HT1A, 5-HT2A, 5-HT2C receptors and other receptor types. Centrally active following oral administration. GR 127935: a 5-HT 1D receptor antagonist | 1,2,4-oxadiazole; benzamides; N-alkylpiperazine; N-arylpiperazine | |
| gr 113808 | GR 113808 : An indolyl carboxylate ester obtained by formal condensation between the carboxy group of 1-methylindole-3-carboxylic acid with the hydroxy group of N-{2-[4-(hydroxymethyl)piperidin-1-yl]ethyl}methanesulfonamide. GR 113808: structure given in first source; a 5-HT(4) receptor antagonist: GR 125487 is the HCl salt | indolyl carboxylate ester; piperidines; sulfonamide | serotonergic antagonist |
| sb 204070a | |||
| docetaxel anhydrous | docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group. Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER. | secondary alpha-hydroxy ketone; tetracyclic diterpenoid | antimalarial; antineoplastic agent; photosensitizing agent |
| piboserod | Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS. | ||
| 3-(piperidine-1-yl)propyl 4-amino-5-chloro-2-methoxybenzoate hydrochloride | 3-(piperidine-1-yl)propyl 4-amino-5-chloro-2-methoxybenzoate hydrochloride: structure given in first source; a 5-HT(4) receptor antagonist | ||
| rs 23597-190 | methoxybenzoic acid | ||
| rs 67333 | RS 67333: 5-HT(4) receptor agonist; structure in first source | aromatic ketone | |
| retinol | all-trans-retinol : A retinol in which all four exocyclic double bonds have E- (trans-) geometry. retinol : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraen-1-ol substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified). vitamin A : Any member of a group of fat-soluble retinoids produced via metabolism of provitamin A carotenoids that exhibit biological activity against vitamin A deficiency. Vitamin A is involved in immune function, vision, reproduction, and cellular communication. Vitamin A: Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. | retinol; vitamin A | human metabolite; mouse metabolite; plant metabolite |
| muramyl dipeptide | glycopeptide | immunological adjuvant | |
| 3-methyl-7-pentyl-8-(2-phenylethylthio)purine-2,6-dione | oxopurine | ||
| tropisetron | tropisetron : An indolyl carboxylate ester obtained by formal condensation of the carboxy group of indole-3-carboxylic acid with the hydroxy group of tropine. Tropisetron: An indole derivative and 5-HT3 RECEPTOR antagonist that is used for the prevention of nausea and vomiting. | indolyl carboxylic acid | |
| 3-methyl-7-(phenylmethyl)-8-(propan-2-ylthio)purine-2,6-dione | oxopurine | ||
| curcumin | curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa. Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. | aromatic ether; beta-diketone; diarylheptanoid; enone; polyphenol | anti-inflammatory agent; antifungal agent; antineoplastic agent; biological pigment; contraceptive drug; dye; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.1.1.25 (shikimate dehydrogenase) inhibitor; EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; flavouring agent; food colouring; geroprotector; hepatoprotective agent; immunomodulator; iron chelator; ligand; lipoxygenase inhibitor; metabolite; neuroprotective agent; nutraceutical; radical scavenger |
| 1-(4-methylphenyl)sulfonyl-2-benzimidazolamine | sulfonamide | ||
| 1-(4-chlorophenyl)sulfonyl-2-benzimidazolamine | sulfonamide | ||
| snap 37889 | |||
| norcisapride | norcisapride: metabolite of cisapride | benzamides | |
| 1-(benzenesulfonyl)-2-benzimidazolamine | sulfonamide | ||
| 1-(4-nitrophenyl)sulfonyl-2-benzimidazolamine | sulfonamide | ||
| prucalopride | prucalopride: a 5-HT4 agonist enterokinetic compound | benzamides | |
| fenretinide | 4-hydroxyphenyl retinamide : A retinoid obtained by formal condensation of the carboxy group of all-trans retinoic acid and the anilino group of 4-hydroxyaniline. Synthetic retinoid agonist. Antiproliferative, antioxidant and anticancer agent with a long half-life in vivo. Apoptotic effects appear to be mediated by a mechanism distinct from that of 'classical' retinoids. Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent. | monocarboxylic acid amide; retinoid | antineoplastic agent; antioxidant |
| 4-amino-5-chloro-N-[(3R,4S)-1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide | benzamides | ||
| ml 10302 | 2-piperidinoethyl 4-amino-5-chloro-2-methoxybenzoate: structure in first source | ||
| pd 166285 | |||
| sb 207710 | SB 207710: structure given in first source | ||
| sb 271046 | SB 271046: 5-HT(6) receptor antagonist; structure in first source | ||
| n-(2-hydroxyethyl)retinamide | N-(2-hydroxyethyl)retinamide: RN given refers to cpd without isomeric designation | ||
| sb 269970 | SB 269970: a 5-HT(7) antagonist; structure in first source | sulfonamide | |
| n-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide | N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide: structure in first source | ||
| brl 24682 | BRL 24682: RN given for (endo)-isomer; structure in first source | ||
| sb258741 | |||
| 4-n-butyl-1-(4-(2-methylphenyl)-4-oxo-1-butyl)-piperidine hydrogen chloride | |||
| sb-656104-a | SB-656104-A: structure in first source | ||
| tafamidis | tafamidis : A member of the class of 1,3-benzoxazoles that is 1,3-benzoxazole-6-carboxylic acid in which the hydrogen at position 2 is replaced by a 3,5-dichlorophenyl group. Used (as its meglumine salt) for the amelioration of transthyretin-related hereditary amyloidosis. tafamidis: may be effective in treating transthyretin amyloid polyneuropathy | 1,3-benzoxazoles; dichlorobenzene; monocarboxylic acid | central nervous system drug |
| barettin | barettin: isolated as a Z/E mixture from sponge Geodia barretti; structure in first source | organic molecular entity | |
| naluzotan | naluzotan: an antidepressant and anti-anxiety agent; structure in first source | ||
| td-5108 | TD-5108: a selective 5-HT(4) receptor agonist with high intrinsic activity; structure in first source | ||
| 1-(4-methoxyphenyl)sulfonyl-2-benzimidazolamine | sulfonamide | ||
| 5,6-dimethyl-1-(4-methylphenyl)sulfonyl-2-benzimidazolamine | sulfonamide | ||
| idarucizumab | |||
| donecopride | donecopride: a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment; structure in first source | ||
| clozapine | clozapine : A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatric disorders like schizophrenia. Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. | benzodiazepine; N-arylpiperazine; N-methylpiperazine; organochlorine compound | adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; GABA antagonist; histamine antagonist; muscarinic antagonist; second generation antipsychotic; serotonergic antagonist; xenobiotic |
| tegaserod | tegaserod: a nonbenzamide 5-hydroxytryptamine(4) agonist; used in treatment of irritable bowel syndrome; marketing suspended 2007 in US due to higher incidence of MI, stroke, and unstable angina; structure given in first source | carboxamidine; guanidines; hydrazines; indoles | gastrointestinal drug; serotonergic agonist |