negative regulation of endothelial cell-matrix adhesion via fibronectin

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of endothelial cell-matrix adhesion via fibronectin. [GO_REF:0000058, GOC:bc, GOC:BHF, GOC:BHF_miRNA, GOC:TermGenie, PMID:19460962]

Negative regulation of endothelial cell-matrix adhesion via fibronectin is a complex process that involves the coordinated action of various cellular signaling pathways and protein interactions. It plays a crucial role in maintaining vascular integrity and regulating blood flow.

**Fibronectin's Role:**

* Fibronectin is a large glycoprotein that serves as a key component of the extracellular matrix (ECM) in various tissues, including the endothelium. It mediates cell adhesion, migration, and differentiation by interacting with integrin receptors on cell surfaces.
* In the context of endothelial cell-matrix adhesion, fibronectin acts as a bridge between the endothelial cells and the ECM.

**Negative Regulation Mechanism:**

1. **Integrin Signaling:**
* Integrins are transmembrane receptors that bind to ECM components like fibronectin.
* Binding of fibronectin to integrins on endothelial cells triggers intracellular signaling cascades.
* These signaling pathways can promote adhesion, migration, and survival of endothelial cells.

2. **Downregulation of Integrin Expression:**
* Negative regulation can occur by reducing the expression levels of integrins on the endothelial cell surface.
* This can be achieved through various mechanisms, including:
* **Transcriptional regulation:** Repression of integrin gene expression by transcription factors.
* **Post-transcriptional regulation:** MicroRNAs and other RNA-binding proteins can target integrin mRNA for degradation or translation inhibition.

3. **Disruption of Integrin-Fibronectin Interaction:**
* Some factors can directly interfere with the interaction between integrins and fibronectin, weakening the adhesion.
* **Competitive inhibitors:** Molecules can bind to the fibronectin-binding site on integrins, blocking the interaction.
* **Proteolytic cleavage:** Enzymes like matrix metalloproteinases (MMPs) can degrade fibronectin, reducing its availability for binding.

4. **Signal Transduction Pathways:**
* Negative regulation can also involve the activation of intracellular signaling pathways that counteract the adhesive signals initiated by integrin-fibronectin interactions.
* For example, the RhoA signaling pathway can promote cell detachment by altering cytoskeletal dynamics.

**Physiological Significance:**

* Negative regulation of endothelial cell-matrix adhesion is essential for maintaining vascular permeability and allowing the passage of fluids and cells through the endothelial barrier.
* This process is also crucial for processes like angiogenesis (new blood vessel formation) and wound healing, where controlled detachment of endothelial cells is required.

**Implications for Disease:**

* Dysregulation of endothelial cell-matrix adhesion can contribute to various pathological conditions:
* **Vascular diseases:** Inappropriate adhesion or detachment can lead to vascular leakage, thrombosis, and atherosclerosis.
* **Cancer:** Tumor cells can exploit alterations in adhesion pathways to invade surrounding tissues and metastasize.

**Conclusion:**

Negative regulation of endothelial cell-matrix adhesion via fibronectin is a complex and tightly regulated process. It is essential for maintaining vascular homeostasis and plays a critical role in a wide range of physiological and pathological processes. Understanding the intricate mechanisms involved in this process is crucial for developing novel therapeutic strategies targeting vascular diseases and other related conditions.'
"

Proteins (1)

Compounds (15)