Target intelligence / Profile preview

Activated fibroblast and myofibroblast (CAF)

Target
CAF
Molecular classification
Other
01

Overview

Activated fibroblasts and myofibroblasts are specialized mesenchymal cells that play a central role in tissue repair and pathological fibrosis (Hinz et al., 2007, PubMed: 17664315). Upon injury or stimulation by growth factors like TGF-β, quiescent fibroblasts undergo a phenotypic transition into activated myofibroblasts, characterized by the expression of alpha-smooth muscle actin (α-SMA) and increased contractile capacity (Gabbiani, 2003, PubMed: 12928694). These cells are the primary producers of extracellular matrix (ECM) components, such as collagen and fibronectin, and they secrete various cytokines and growth factors that modulate the microenvironment (Wynn, 2008, PubMed: 18846103). In chronic diseases, persistent activation leads to excessive ECM deposition, resulting in organ dysfunction and fibrosis across the lung, liver, and kidney (Rockey et al., 2015, PubMed: 25830682). In oncology, cancer-associated fibroblasts (CAFs) contribute to tumor growth, immunosuppression, and drug resistance (Sahai et al., 2020, PubMed: 31900450). Therapeutic strategies targeting these cells include inhibiting activation pathways like TGF-β or PDGF signaling (e.g., Nintedanib), or direct depletion using cell-surface markers like Fibroblast Activation Protein (FAP) (Lindner et al., 2019, PubMed: 31171636).

Other names
MyofibroblastCancer-associated fibroblastActivated mesenchymal cellα-SMA-positive fibroblast
02

Mechanism of action

Inhibition of pro-fibrotic signaling pathways (TGF-beta, PDGF, FGF), direct depletion of activated cell populations via surface markers (e.g., FAP), and inhibition of extracellular matrix cross-linking enzymes.

03

Biological functions

Extracellular matrix organizationWound healingCell contractilityCytokine productionTissue remodeling
04

Disease associations

FibrosisCancerCardiovascular diseaseInflammation
05

Safety considerations

Impaired wound healingOff-target effects on healthy mesenchymal cellsPotential for paradoxical tumor promotionSystemic fibrosis inhibition risks
06

Interacting drugs

Nintedanib

4 more in the full profile.

07

Biomarkers

Alpha-smooth muscle actin (α-SMA)Fibroblast activation protein (FAP)Platelet-derived growth factor receptor beta (PDGFR-beta)VimentinCollagen type I

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