negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
Definition
Target type: biologicalprocess
Any process that decreases the rate, frequency or extent of the transition where a mesenchymal cell establishes apical/basolateral polarity,forms intercellular adhesive junctions, synthesizes basement membrane components and becomes an epithelial cell that will contribute to the shaping of the metanephros. [GOC:dph, GOC:yaf]
Negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis is a crucial biological process during kidney development. Metanephros, the permanent kidney in mammals, arises from reciprocal interactions between two distinct tissues: the metanephric mesenchyme and the ureteric bud. The metanephric mesenchyme, derived from the intermediate mesoderm, is composed of undifferentiated mesenchymal cells. These mesenchymal cells undergo epithelialization, transforming into epithelial cells that form the nephrons, the functional units of the kidney. This transition, termed mesenchymal to epithelial transition (MET), is tightly regulated by various signaling pathways and transcription factors. Negative regulation of MET ensures that this process occurs in a controlled and spatially restricted manner, preventing uncontrolled epithelialization and ensuring proper kidney formation. The precise mechanisms underlying this negative regulation are complex and involve a interplay of several factors:
- **BMP signaling:** Bone morphogenetic proteins (BMPs) are secreted signaling molecules known to inhibit MET in the metanephric mesenchyme. BMP signaling promotes mesenchymal cell survival and prevents premature differentiation into epithelial cells.
- **Wnt signaling:** Wnt signaling pathways, particularly Wnt4, are also involved in negative regulation of MET. Wnt4 acts as a repressor of epithelial differentiation, maintaining mesenchymal cell fate and preventing premature epithelialization.
- **Slit-Robo signaling:** The Slit-Robo signaling pathway is another important regulator of MET. Slit proteins, secreted from the ureteric bud, bind to Robo receptors on mesenchymal cells, repressing MET and promoting mesenchymal cell migration towards the ureteric bud.
- **Transcription factors:** Several transcription factors are involved in regulating MET, including Pax2, Six2, and Osr1. These factors maintain mesenchymal cell fate and suppress epithelialization, contributing to the negative regulation of MET.
Overall, negative regulation of MET is a critical process for proper metanephros morphogenesis. It ensures that the metanephric mesenchyme remains in a mesenchymal state until appropriate signals from the ureteric bud trigger MET and nephron formation. This fine-tuned regulation ensures the correct timing and spatial arrangement of epithelial cells, leading to the development of a functional kidney.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Signal transducer and activator of transcription 1-alpha/beta | A signal transducer and activator of transcription 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P42224] | Homo sapiens (human) |
| Catenin beta-1 | A catenin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35222] | Homo sapiens (human) |
Compounds (12)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| suramin sodium | suramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness. | organic sodium salt | angiogenesis inhibitor; antinematodal drug; antineoplastic agent; apoptosis inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; GABA antagonist; GABA-gated chloride channel antagonist; purinergic receptor P2 antagonist; ryanodine receptor agonist; trypanocidal drug |
| epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
| salvin | salvin: a biocyclic diterpenoid; from sage and rosemary (Lamiaceae) | abietane diterpenoid; carbotricyclic compound; catechols; monocarboxylic acid | angiogenesis modulating agent; anti-inflammatory agent; antineoplastic agent; antioxidant; apoptosis inducer; food preservative; HIV protease inhibitor; plant metabolite |
| toxoflavin | toxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7. toxoflavin: azapteridine antibiotic; structure | carbonyl compound; pyrimidotriazine | antibacterial agent; antineoplastic agent; apoptosis inducer; bacterial metabolite; toxin; virulence factor; Wnt signalling inhibitor |
| nsc 74859 | NSC 74859: inhibits Stat3 binding activity; structure in first source S3I-201 : An amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid. | amidobenzoic acid; monohydroxybenzoic acid; tosylate ester | STAT3 inhibitor |
| cercosporin | cercosporin : An organic heterohexacyclic compound that is perylo[1,12-def][1,3]dioxepine-6,11-dione substituted by hydroxy groups at positions 5 and 12, by methoxy groups at positions 7 and 10, and by 2-hydroxypropyl groups at positions 8 and 9 (the R,R-stereoisomer). It is a phytotoxin which was first isolated from the pathogenic soybean fungus, Cercospora kikuchii and later found in multiple members of the genus Cercospora. cercosporin: phyytotoxin from Cercospora beticola Sacc; posses photodynamic action on mice, bacteria & plants | ||
| LSM-42773 | aromatic ketone | ||
| etodolac, (-)-isomer | (R)-etodolac : The R-enantiomer of etodolac. It is inactive, in contrast to the enantiomer, (S)-etodolac, which is a preferential inhibitor of cyclo-oxygenase 2 and a non-steroidal anti-inflammatory. The racemate is commonly used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. | etodolac | |
| nf 449 | |||
| 5,15-diphenylporphine | 5,15-diphenylporphine: structure in first source | ||
| ucn 1028 c | calphostin C: structure given in first source; isolated from Cladosporium cladosporioides | ||
| guttiferone k | guttiferone K: antiproliferative compound of Rheedia calcicola from the Madagascar rain forest; structure in first source |