epithelial to mesenchymal transition involved in cardiac fibroblast development
Definition
Target type: biologicalprocess
A transition where an epicardial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell that will mature into a cardiac fibroblast. [GOC:mtg_heart]
Epithelial-to-mesenchymal transition (EMT) is a fundamental biological process crucial for cardiac fibroblast development. It involves a phenotypic switch of epithelial cells, characterized by cell-cell junctions and apical-basal polarity, into mesenchymal cells, displaying migratory and invasive capabilities. This transition is essential for the formation of the heart during embryogenesis and contributes to cardiac fibrosis in response to injury.
During EMT in cardiac fibroblast development, epithelial cells undergo significant changes in their morphology, gene expression, and behavior. Key molecular events include:
1. **Loss of cell-cell adhesion:** Epithelial cells exhibit tight junctions and adherens junctions, maintaining cell-cell contact. During EMT, these junctions are disrupted, mediated by downregulation of cell adhesion molecules such as E-cadherin and upregulation of N-cadherin.
2. **Acquisition of migratory and invasive capabilities:** EMT promotes mesenchymal characteristics, including increased motility and the ability to penetrate surrounding tissues. This is achieved through upregulation of matrix metalloproteinases (MMPs), enzymes that degrade the extracellular matrix, allowing for cell migration.
3. **Changes in gene expression:** EMT involves a complex interplay of transcription factors and signaling pathways. Key transcription factors driving EMT include Snail, Slug, Twist, and Zeb1/2. These factors repress epithelial genes and activate mesenchymal genes, further promoting the transition.
4. **Increased fibroblast differentiation:** EMT facilitates the differentiation of mesenchymal cells into fibroblasts. Fibroblasts play critical roles in collagen synthesis and scar formation, contributing to tissue repair.
5. **Contribution to cardiac fibrosis:** Following cardiac injury, such as myocardial infarction, EMT is triggered, leading to an influx of fibroblasts and excessive collagen deposition, resulting in scar formation. This process, known as cardiac fibrosis, can impair heart function and contribute to heart failure.
In summary, EMT is a complex and highly regulated process that plays a vital role in cardiac fibroblast development. It involves the loss of epithelial characteristics, acquisition of mesenchymal properties, and subsequent differentiation into fibroblasts. While essential for embryonic heart development, EMT also contributes to pathological fibrosis in the adult heart. Understanding the molecular mechanisms underlying EMT is crucial for developing therapeutic strategies to prevent or reverse cardiac fibrosis.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Programmed cell death protein 4 | A programmed cell death protein 4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q53EL6] | Homo sapiens (human) |
Compounds (2)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tubercidin | tubercidin : An N-glycosylpyrrolopyrimidine that is adenosine in which the in the 5-membered ring that is not attached to the ribose moiety is replaced by a carbon. Tubercidin is produced in the culture broth of Streptomyces tubericidus. Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids. | antibiotic antifungal agent; N-glycosylpyrrolopyrimidine; ribonucleoside | antimetabolite; antineoplastic agent; bacterial metabolite |
| sirolimus | sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent. Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. | antibiotic antifungal drug; cyclic acetal; cyclic ketone; ether; macrolide lactam; organic heterotricyclic compound; secondary alcohol | antibacterial drug; anticoronaviral agent; antineoplastic agent; bacterial metabolite; geroprotector; immunosuppressive agent; mTOR inhibitor |