Target type: biologicalprocess
Any process that stops, prevents, or reduces the frequency, rate or extent of smooth muscle cell-matrix adhesion. [GOC:BHF]
Negative regulation of smooth muscle cell-matrix adhesion involves a complex interplay of molecular mechanisms that modulate the interaction between smooth muscle cells (SMCs) and the extracellular matrix (ECM). This process is critical for maintaining tissue integrity, regulating vascular tone, and controlling cell migration during development and wound healing. Here's a detailed description:
**1. ECM Composition and Adhesion Receptors:**
- The ECM provides structural support and serves as a signaling platform for SMCs. Major ECM components include collagen, elastin, fibronectin, and laminin.
- SMCs adhere to the ECM via integrin receptors, transmembrane proteins that bind to specific ECM components. Integrins link the ECM to the cytoskeleton, transmitting signals that regulate cell behavior.
**2. Signaling Pathways:**
- Upon ECM binding, integrins activate intracellular signaling pathways, including the focal adhesion kinase (FAK) pathway and the Rho GTPase pathway.
- **FAK pathway:** FAK phosphorylation triggers downstream signaling cascades, leading to cytoskeletal reorganization, cell migration, and proliferation.
- **Rho GTPase pathway:** Rho GTPases, such as RhoA, Rac1, and Cdc42, regulate actin cytoskeleton dynamics and control cell adhesion and migration.
**3. Negative Regulation Mechanisms:**
- **Downregulation of Integrin Expression:** SMCs can downregulate integrin expression, reducing their ability to bind to the ECM. This can be mediated by various factors, including cytokines and growth factors.
- **Inhibition of Integrin Activation:** Certain signaling molecules, such as phosphatases, can dephosphorylate integrins, preventing their activation and ECM binding.
- **Disruption of Focal Adhesion Formation:** Factors like calpain and other proteases can degrade focal adhesion components, weakening the link between the ECM and the cytoskeleton.
- **Modulation of Cytoskeleton Dynamics:** Proteins like cofilin can depolymerize actin filaments, disrupting the cytoskeletal structure required for stable adhesion.
- **Cytokine Signaling:** Cytokines, such as TGF-β, can promote ECM degradation and inhibit SMC adhesion.
**4. Physiological Implications:**
- Negative regulation of SMC-matrix adhesion plays a crucial role in:
- **Vascular Remodeling:** During blood vessel development and disease processes, SMC migration and adhesion are precisely controlled.
- **Wound Healing:** SMC migration and adhesion are essential for wound repair and tissue regeneration.
- **Atherosclerosis:** Dysregulation of SMC adhesion contributes to plaque formation in atherosclerosis.
- **Cancer Metastasis:** SMC adhesion and migration can be altered during cancer metastasis, facilitating tumor cell dissemination.
**5. Therapeutic Potential:**
- Understanding the mechanisms of negative regulation of SMC-matrix adhesion has potential therapeutic implications in treating cardiovascular diseases, wound healing disorders, and cancer metastasis.
- Drugs targeting specific components of the adhesion pathways could be developed to modulate SMC behavior and improve clinical outcomes.'
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Protein | Definition | Taxonomy |
---|---|---|
Plasminogen activator inhibitor 1 | A plasminogen activator inhibitor 1 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P05121] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
gallic acid | gallate : A trihydroxybenzoate that is the conjugate base of gallic acid. | trihydroxybenzoic acid | antineoplastic agent; antioxidant; apoptosis inducer; astringent; cyclooxygenase 2 inhibitor; EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor; geroprotector; human xenobiotic metabolite; plant metabolite |
hexachlorophene | hexachlorophene : An organochlorine compound that is diphenylmethane in which each of the phenyl groups is substituted by chlorines at positions 2, 3, and 5, and by a hydroxy group at position 6. An antiseptic that is effective against Gram-positive organisms, it is used in soaps and creams for the treatment of various skin disorders. It is also used in agriculture as an acaricide and fungicide, but is not approved for such use within the European Union. Hexachlorophene: A chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is mainly used in soaps and creams and is an ingredient of various preparations used for skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797) | bridged diphenyl fungicide; polyphenol; trichlorobenzene | acaricide; antibacterial agent; antifungal agrochemical; antiseptic drug |
1,2,5,8-tetrahydroxy anthraquinone | 1,2,5,8-tetrahydroxy anthraquinone: structure in first source quinalizarin : A tetrahydroxyanthraquinone having the four hydroxy groups at the 1-, 2-, 5- and 8-positions. | tetrahydroxyanthraquinone | EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor |
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 |
sennoside A | sennoside A : A member of the class of sennosides that is rel-(9R,9'R)-9,9',10,10'-tetrahydro-9,9'-bianthracene-2,2'-dicarboxylic acid which is substituted by hydroxy groups at positions 4 and 4', by beta-D-glucopyranosyloxy groups at positions 5 and 5', and by oxo groups at positions 10 and 10'. The exact stereochemisty at positions 9 and 9' is not known - it may be R,R (as shown) or S,S. | oxo dicarboxylic acid; sennosides | |
Epigallocatechin 3,5-Digallate | catechin | ||
pai 039 | tiplaxtinin: inhibitor of plasminogen activator inhibitor-1 | indole-3-acetic acids | |
xr 334 | XR 334: a low molecular weight modulator of human plasminogen activator inhibitor-1 activity; structure given in first source; RN given refers to (Z,Z)-isomer | ||
sideroxylonal c | sideroxylonal C: formylated phloroglucinol from flowers of Eucalyptus albens; structure in first source |