Fibroblast differentiation

November 15, 2023

Fibroblasts are a type of biological cell found in connective tissue. They are the principal active cells of connective tissue and play a critical role in synthesizing the extracellular matrix and collagen, which are essential for providing the structural framework (stroma) for animal tissues. Fibroblasts are large, flat, elongated (spindle-shaped) cells that produce tropocollagen, the forerunner of collagen, and ground substance, an amorphous gel-like matrix that fills the spaces between cells and fibers in connective tissue. These cells are also involved in wound healing, as they migrate to the site of damage and deposit new collagen to facilitate the healing process. Fibroblasts are the most common type of cell found in connective tissue and are derived from primitive mesenchyme.

The differentiation of fibroblasts into myofibroblasts, a process associated with tissue repair and fibrosis, is regulated by various cytokines and signaling pathways. Some of the key regulators of fibroblast differentiation include:

  1. Connective Tissue Growth Factor (CTGF): Different domains of the CTGF protein are responsible for mediating the proliferation and differentiation of fibroblasts
  2. Fibroblast Growth Factors (FGFs): FGFs, such as FGFa and FGFb, are secreted by various cell types, including fibroblasts, and play a role in the recruitment, activation, mitogenesis, migration, and differentiation of various cell types, including fibroblasts
  3. Transforming Growth Factor-β (TGF-β): TGF-β signaling is a key regulator of myofibroblast differentiation and extracellular matrix protein expression
  4. Ancillary Signaling Events: Various ancillary signaling events, such as the Notch signaling pathway, YB-1, NF-κB, and PPARγ, may also play a role in the regulation of fibroblast differentiation and myofibroblast phenotype

The above factors and signaling pathways are involved in the complex regulation of fibroblast differentiation and the transition to the myofibroblast phenotype, which has implications for tissue repair, fibrosis, and potential clinical therapies targeting fibroblasts.

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