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Review

07 March 2025

Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and fatal disease with an increasing incidence and limited therapeutic options. It is characterized by the formation and deposition of excess extracellular matrix proteins resulting in the gradual replacement of normal lung architecture by fibrous tissue. The cellular and molecular mechanism of IPF has not been fully understood. A hallmark in IPF is pulmonary fibroblast to myofibroblast transformation (FMT). During excessive lung repair upon exposure to harmful stimuli, lung fibroblasts transform into myofibroblasts under stimulation of cytokines, chemokines, and vesicles from various cells. These mediators interact with lung fibroblasts, initiating multiple signaling cascades, such as TGFβ1, MAPK, Wnt/β-catenin, NF-κB, AMPK, endoplasmic reticulum stress, and autophagy, contributing to lung FMT. Furthermore, single-cell transcriptomic analysis has revealed significant heterogeneity among lung myofibroblasts, which arise from various cell types and are adapted to the altered microenvironment during pathological lung repair. This review provides an overview of recent research on the origins of lung myofibroblasts and the molecular pathways driving their formation, with a focus on the interactions between lung fibroblasts and epithelial cells, endothelial cells, and macrophages in the context of lung fibrosis. Based on these molecular insights, targeting the lung FMT could offer promising avenues for the treatment of IPF.

Keywords: Pulmonary fibrosis; Extracellular matrix; Fibroblasts; Myofibroblasts; Cytokines

Communication

21 March 2023

Established Hepatic Stellate Cell Lines in Hepatology Research

Hepatic stellate cells comprise a minor cell population in the liver, playing a key role in the pathogenesis of hepatic fibrosis. In chronic liver damage, these cells undergo a transition from a quiescent to a highly proliferative phenotype with the capacity to synthesize large quantities of extracellular matrix compounds such as collagens. Because of their pivotal role in liver disease pathogenesis, this hepatic cell population has become the focus of liver research for many years. However, the isolation of these cells is time consuming and requires the trained laboratory personnel. In addition, working with primary cells requires the following of ethical and legal standards and potentially needs the approval from respective authorities. Therefore, continuous growing hepatic stellate cells have become very popular in research laboratories because they are widely available and easy to handle, and allow a continuous supply of materials, and further reduction of lab animal use in biomedical research. This communication provides some general information about immortalized hepatic stellate cell lines from mouse, rats and humans.

Keywords: Cell culture; Cell lines; Hepatic stellate cells; Myofibroblasts; Liver; Fibrosis; In vitro; Translational research
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