Pathogenic mechanisms involved in fibrosis of various organs share many common features. Myofibroblasts are thought to
play a major role in fibrosis through excessive deposition of extracellular matrix during wound healing processes. Myofibroblasts are observed
in fibrotic lesions, and whereas these derive from the hepatic stellate cells in liver, in lung they appear to originate from fibroblasts.
The source of these fibroblasts has been the object of numerous studies over the recent years and points towards multiple sources.
First of all, resident fibroblasts are thought to differentiate into the more contractile myofibroblasts, secreting many extracellular matrix
proteins. Secondly, the epithelial to mesenchymal transition (EMT) of epithelial cells may also account for increased numbers of fibroblasts,
though in vivo evidence in patient tissue.is still scarce. Thirdly, the enigmatic fibrocytes, stemming from the bone marrow, may
also account for increasing numbers of fibroblasts in fibrotic lesions. These pathogenic processes are further augmented by the generation
of so-called alternatively activated macrophages, which have direct and indirect effects on myofibroblast accumulation and collagen
deposition. TGFβ, which is produced predominantly by macrophages, plays a central role in all these processes by inducing EMT, driving
differentiation of fibrocytes, and differentiation towards myofibroblasts.
This review describes the potential origins and roles of these fibrotic cells in the lung and discusses models to study these cells in vitro.
These models offer innovative approaches in target and drug discovery, aiming to uncover novel therapeutic targets that regulate the profibrotic
phenotype of these cells.
Keywords: Fibrosis, IPF, EMT, epithelial cell, fibroblasts, fibrocytes, macrophages, TGFβ, Myofibroblasts, collagen.
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