negative regulation of collagen biosynthetic process

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of collagen, any of a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. [GOC:mah]

Negative regulation of collagen biosynthetic process is a complex biological process that controls the production of collagen, a major structural protein in the extracellular matrix (ECM). Collagen is essential for maintaining the integrity of tissues and organs, and its dysregulation can lead to a variety of diseases, including fibrosis, cancer, and vascular disorders.

This process involves a multifaceted interplay of regulatory mechanisms, including:

* **Transcriptional regulation:** Transcription factors and signaling pathways can modulate the expression of genes encoding collagen proteins, such as COL1A1 and COL1A2.
* **Post-translational modifications:** After synthesis, collagen proteins undergo a series of post-translational modifications, including hydroxylation, glycosylation, and proteolytic processing, which are crucial for their proper folding, assembly, and secretion. These modifications can be regulated by enzymes like prolyl hydroxylases and lysyl hydroxylases, which can be targeted by specific regulatory pathways.
* **ECM assembly:** Collagen molecules self-assemble into fibrils that form the ECM. The assembly process is influenced by factors like ECM components, chaperone proteins, and proteases.
* **Cellular signaling:** Cells can sense changes in ECM composition and respond by altering their behavior, including collagen production. This feedback loop involves signaling pathways like TGF-beta and Wnt pathways, which can regulate both collagen biosynthesis and ECM remodeling.

Negative regulation of collagen biosynthesis can occur at various levels:

* **Inhibition of transcription:** Specific transcription factors, like the Snail family of repressors, can bind to the promoters of collagen genes, suppressing their transcription.
* **Modulation of post-translational modifications:** Enzymes like lysyl oxidase can crosslink collagen molecules, leading to ECM stiffening and reduced collagen production.
* **ECM degradation:** Matrix metalloproteinases (MMPs) can break down collagen fibers, reducing the overall ECM content and regulating collagen biosynthesis.
* **Cellular signaling pathways:** Inhibitors of TGF-beta signaling can suppress collagen production, while activation of Wnt signaling can promote collagen degradation.

The precise mechanisms of negative regulation of collagen biosynthesis vary depending on the specific cell type, tissue, and physiological context. However, understanding the regulatory pathways involved is crucial for developing therapeutic interventions for diseases related to aberrant collagen production.'
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Proteins (2)

Compounds (3)