negative regulation of smooth muscle cell-matrix adhesion

Definition

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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Proteins (1)

Compounds (9)