transforming growth factor beta production

Definition

Target type: biologicalprocess

The appearance of any member of the transforming growth factor-beta family of cytokines due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Transforming growth factor-beta family members include TGF-B1, TGF-B2, and TGF-B3. [GOC:add, GOC:rv, PMID:16891311, PMID:2022183]

Transforming growth factor beta (TGF-β) production is a complex and tightly regulated process that involves multiple cellular signaling pathways and molecular events. TGF-β exists as a latent complex, comprised of a dimeric TGF-β protein bound to a latency-associated protein (LAP). This latent complex is secreted from the cell and remains inactive until activated.

TGF-β activation can occur through various mechanisms:

* **Proteolytic cleavage:** Specific proteases, such as plasmin, MMPs (matrix metalloproteinases), and thrombospondin-1, can cleave LAP, releasing active TGF-β.
* **Integrin-mediated activation:** Integrins, cell surface receptors that bind to extracellular matrix proteins, can interact with LAP and trigger conformational changes that expose the active TGF-β.
* **Acidification:** Changes in pH can disrupt the interaction between TGF-β and LAP, leading to activation.
* **Mechanical stress:** Physical forces, such as shear stress or pressure, can also activate TGF-β.

Once activated, TGF-β can bind to its receptors, TGF-β receptors I and II, on target cells. This binding triggers a cascade of intracellular signaling events, including phosphorylation of downstream signaling molecules, such as Smad proteins. Activated Smads translocate to the nucleus, where they regulate the transcription of target genes involved in various cellular processes, including:

* **Cell proliferation and differentiation:** TGF-β plays a crucial role in regulating cell growth, differentiation, and apoptosis.
* **Extracellular matrix production:** TGF-β promotes the synthesis and deposition of extracellular matrix components, contributing to tissue repair and remodeling.
* **Immune regulation:** TGF-β is a potent immunosuppressive cytokine that modulates immune responses and maintains immune homeostasis.

The production of TGF-β is influenced by a variety of factors, including:

* **Cellular stress:** Factors such as oxidative stress, hypoxia, and DNA damage can stimulate TGF-β production.
* **Cytokines and growth factors:** Other cytokines and growth factors, such as TNF-α, IL-1β, and PDGF, can induce TGF-β expression.
* **Environmental stimuli:** Factors like ultraviolet radiation, mechanical stress, and microbial infections can trigger TGF-β production.

Dysregulation of TGF-β production and signaling is implicated in various pathological conditions, including cancer, fibrosis, autoimmune diseases, and developmental disorders. Therefore, understanding the mechanisms of TGF-β production and regulation is crucial for developing targeted therapies for these diseases.'
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Proteins (2)

Compounds (22)