The hard problem: Mechanotransduction perpetuates the myofibroblast phenotype in scleroderma fibrosis.
Andrew LeaskPublished in: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (2021)
The effector cells ultimately responsible for fibrosis are myofibroblasts. In the fibrotic autoimmune connective tissue disease scleroderma, myofibroblasts are autonomously activated, and retain their phenotype upon culturing. Since the 1990s, researchers have exploited this fact to use scleroderma fibroblasts as a model system to uncover the fundamental mechanisms underlying myofibroblast persistence in fibrotic conditions. These studies have suggested that an autocrine transforming growth factor (TGF)beta signaling loop is insufficient to explain the persistent myofibroblast phenotype but instead support the hypothesis that fibrotic myofibroblasts possess an intrinsically activated pro-adhesive signaling pathway, and that this contributes to the perpetuation of pathological fibrosis. This review focuses on these observations.
Keyphrases
- transforming growth factor
- systemic sclerosis
- epithelial mesenchymal transition
- interstitial lung disease
- signaling pathway
- induced apoptosis
- idiopathic pulmonary fibrosis
- cell cycle arrest
- pi k akt
- multiple sclerosis
- transcription factor
- endoplasmic reticulum stress
- oxidative stress
- cell death
- rheumatoid arthritis
- cell proliferation
- type iii