Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of aortic smooth muscle cell differentiation. [GO_REF:0000058, GOC:BHF, GOC:BHF_miRNA, GOC:rph, GOC:TermGenie, PMID:22034194]
Positive regulation of aortic smooth muscle cell differentiation is a complex biological process involving intricate signaling pathways and transcriptional networks that promote the transition of undifferentiated mesenchymal cells into mature, contractile smooth muscle cells. This process is essential for maintaining the integrity and functionality of the aorta, the largest artery in the body. Here is a detailed description:
1. **Signal Reception and Transduction:**
- **Growth factors and cytokines:** Factors like platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and fibroblast growth factor (FGF) bind to their respective receptors on the surface of mesenchymal cells, triggering intracellular signaling cascades.
- **Mechanical stimuli:** Stretch and shear stress experienced by the aorta due to blood flow can activate mechanosensitive pathways, leading to the activation of transcription factors.
2. **Transcriptional Regulation:**
- **Transcription factors:** Activated signaling pathways converge on transcription factors like myocardin, serum response factor (SRF), and MEF2, which bind to specific DNA sequences in the promoters of target genes.
- **Target genes:** These transcription factors induce the expression of genes encoding key proteins involved in smooth muscle cell differentiation, such as:
- **Contractile proteins:** Smooth muscle actin (α-SMA), myosin heavy chain, and calponin.
- **Cytoskeletal proteins:** Desmin and vimentin.
- **Structural proteins:** Elastin and collagen.
- **Signaling proteins:** RhoA, ROCK, and myosin light chain kinase.
3. **Cell Cycle Control and Proliferation:**
- **Cell cycle arrest:** During differentiation, smooth muscle cells exit the cell cycle and stop dividing, leading to a decrease in proliferation.
- **Cyclin-dependent kinases (CDKs) and cyclins:** These proteins, involved in cell cycle regulation, are downregulated during smooth muscle cell differentiation.
- **Cell cycle inhibitors:** Expression of p21 and p27, cell cycle inhibitors, is upregulated, further promoting cell cycle arrest.
4. **Phenotypic Changes:**
- **Contractile apparatus development:** The expression of contractile proteins leads to the formation of sarcomeres, the functional units of muscle contraction.
- **Cytoskeletal reorganization:** Actin and myosin filaments assemble into organized structures, giving the smooth muscle cell its characteristic contractile properties.
- **Cell morphology:** Smooth muscle cells adopt a spindle-shaped morphology, aligning along the axis of the aorta.
5. **Extracellular Matrix Remodeling:**
- **ECM deposition:** Smooth muscle cells synthesize and secrete components of the extracellular matrix, such as collagen and elastin, which contribute to the structural integrity of the aorta.
- **ECM degradation:** Controlled degradation of ECM components is also necessary for proper vessel remodeling.
6. **Functional Maturation:**
- **Contractility:** Mature smooth muscle cells exhibit robust contractility, responding to vasoconstrictors and vasodilators, thus regulating blood flow.
- **Elasticity:** The elastic properties of smooth muscle cells contribute to the elasticity of the aorta, allowing it to accommodate changes in blood pressure.
7. **Homeostatic Regulation:**
- **Negative feedback loops:** The differentiation process is finely regulated by negative feedback mechanisms, preventing excessive differentiation and maintaining an optimal balance between smooth muscle cell proliferation and differentiation.
- **Environmental cues:** Environmental factors, such as oxygen tension and nutrient availability, can influence the differentiation process.
**Overall, the positive regulation of aortic smooth muscle cell differentiation is a tightly regulated and complex process involving a series of interconnected signaling pathways and transcriptional networks that orchestrate the transition of undifferentiated mesenchymal cells into specialized, contractile smooth muscle cells, ensuring the structural integrity and functional efficiency of the aorta.**'"
Protein | Definition | Taxonomy |
---|---|---|
Cystathionine gamma-lyase | A cystathionine gamma-lyase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P32929] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
aminooxyacetic acid | (aminooxy)acetic acid : A member of the class of hydroxylamines that is acetic acid substituted at postion 2 by an aminooxy group. It is a compound which inhibits aminobutyrate aminotransferase activity in vivo, resulting in increased levels of gamma-aminobutyric acid in tissues. Aminooxyacetic Acid: A compound that inhibits aminobutyrate aminotransferase activity in vivo, thereby raising the level of gamma-aminobutyric acid in tissues. | amino acid; hydroxylamines; monocarboxylic acid | anticonvulsant; EC 2.6.1.19 (4-aminobutyrate--2-oxoglutarate transaminase) inhibitor; EC 4.2.1.22 (cystathionine beta-synthase) inhibitor; nootropic agent |
salicylic acid | Scalp: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL). | monohydroxybenzoic acid | algal metabolite; antifungal agent; antiinfective agent; EC 1.11.1.11 (L-ascorbate peroxidase) inhibitor; keratolytic drug; plant hormone; plant metabolite |
aurintricarboxylic acid | aurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'. Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues. | monohydroxybenzoic acid; quinomethanes; tricarboxylic acid | fluorochrome; histological dye; insulin-like growth factor receptor 1 antagonist |
mesalamine | mesalamine : A monohydroxybenzoic acid that is salicylic acid substituted by an amino group at the 5-position. Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed) | amino acid; aromatic amine; monocarboxylic acid; monohydroxybenzoic acid; phenols | non-steroidal anti-inflammatory drug |
penicillamine | penicillamine : An alpha-amino acid having the structure of valine substituted at the beta position with a sulfanyl group. Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. | non-proteinogenic alpha-amino acid; penicillamine | antirheumatic drug; chelator; copper chelator; drug allergen |
nitroxoline | nitroxoline : A monohydroxyquinoline in which the hydroxy group is positioned at C-8 with a nitro group trans to it at C-5. nitroxoline: structure in Merck Index, 9th ed, #6475; RN given refers to parent cpd | C-nitro compound; monohydroxyquinoline | antifungal agent; antiinfective agent; antimicrobial agent; renal agent |
olsalazine | olsalazine : An azobenzene that consists of two molecules of 4-aminosalicylic acid joined by an azo linkage. A prodrug for mesalazine, an anti-inflammatory drug, it is used (as the disodium salt) in the treatment of inflammatory bowel disease. olsalazine: cpd with 2 salicylate molecules linked together by an azo bond | azobenzenes; dicarboxylic acid | non-steroidal anti-inflammatory drug; prodrug |
methyldopa | alpha-methyl-L-dopa : A derivative of L-tyrosine having a methyl group at the alpha-position and an additional hydroxy group at the 3-position on the phenyl ring. Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. | L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | alpha-adrenergic agonist; antihypertensive agent; hapten; peripheral nervous system drug; sympatholytic agent |
6-amino-7-chloro-5,8-dioxoquinoline | 6-amino-7-chloro-5,8-dioxoquinoline: quinone structure important in this cpd; structure | ||
kalafungin | kalafungin: nanaomycin D from Streptomyces rosa & is enantiomer of kalafungin; RN given refers to (3aR-(3aalpha,5alpha,11balpha))-isomer; see also nanaomycin C; structure of kalafungin in first source; structure of nanaomycin in second source | ||
nsc228155 | |||
agathisflavone | agathisflavone : A biflavonoid that is obtained by oxidative coupling of two molecules of apigenin resulting in a bond between positions C-6 and C-8 of the two chromene rings. agathisflavone: bis-apigenin coupled at 6 and 8 positions; isolated from the plant Canarium manii; has hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity | biaryl; biflavonoid; hydroxyflavone | antineoplastic agent; antiviral agent; hepatoprotective agent; metabolite |
cupressuflavone | cupressuflavone : A biflavonoid that is obtained by oxidative coupling of two molecules of apigenin resulting in a bond between positions C-8 of the two chromene rings respectively. Isolated from Cupressus sempervirens and Juniperus occidentalis, it exhibits free radical scavenging and antielastase activities. cupressuflavone: from Cupressus macrocarpa; structure in first source | biflavonoid; hydroxyflavone; ring assembly | EC 3.4.21.37 (leukocyte elastase) inhibitor; metabolite; radical scavenger |
podocarpusflavone a | podocarpusflavone A: isolated from Podocarpus imbricatus | flavonoid oligomer | |
aminoethoxyvinylglycine | aminoethoxyvinylglycine: RN given for (S-(E))-isomer |