Found 4 results
Review
07 March 2025Mechanisms 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.
Review
22 November 2024Dermal Fibrosis and the Current Scope of Hydrogel Strategies for Scarless Wound Healing
Dermal fibrosis poses a significant challenge in wound healing, affecting both the appearance and functionality of the scarred skin tissue. Beyond aesthetic implications, fibrosis can lead to pruritus, chronic pain, loss of mechanical flexibility, and impeded restoration of skin appendages, blood vessels, and nerves. Therefore, scar prevention remains a priority in wound management, and hydrogels, with their hydrophilic three-dimensional network and extracellular matrix-mimicking properties, have emerged as promising biomaterials for achieving scarless wound regeneration. In this review, we explore advancements in various hydrogel strategies designed to regulate myofibroblast differentiation, control the wound microenvironment, and mitigate dermal fibrosis. We provide an overview of dermal fibrosis, the scar-forming cells involved, and the various types of dermal scars. We then summarise advancements made in antifibrotic hydrogel formulations, emphasizing their practical applications in scarless skin wound healing. By reviewing the current research landscape and highlighting key hydrogel-based biomaterial strategies employed in this field, we aim to offer insights into design principles and underlying mechanisms of action. We intend for this review to serve as a valuable resource for researchers and clinicians interested in entering this field or exploring the potential of hydrogels to promote scarless wound healing.
Review
21 December 2023TANGO1 Dances to Export of Procollagen from the Endoplasmic Reticulum
The endoplasmic reticulum (ER) to Golgi secretory pathway is an elegantly complex process whereby protein cargoes are manufactured, folded, and distributed from the ER to the cisternal layers of the Golgi stack before they are delivered to their final destinations. The export of large bulky cargoes such as procollagen and its trafficking to the Golgi is a sophisticated mechanism requiring TANGO1 (Transport ANd Golgi Organization protein 1. It is also called MIA3 (Melanoma Inhibitory Activity protein 3). TANGO1 has two prominent isoforms, TANGO1-Long and TANGO1-Short, and each isoform has specific functions. On the luminal side, TANGO1-Long has an HSP47 recruitment domain and uses this protein to collect collagen. It can also tether its paralog isoforms cTAGE5 and TALI and along with these proteins enlarges the vesicle to accommodate procollagen. Recent studies show that TANGO1-Long combines retrograde membrane flow with anterograde cargo transport. This complex mechanism is highly activated in fibrosis and promotes the excessive deposition of collagen in the tissues. The therapeutic targeting of TANGO1 may prove successful in the control of fibrotic disorders. This review focuses on TANGO1 and its complex interaction with other procollagen export factors that modulate increased vesicle size to accommodate the export of procollagen.
Communication
21 March 2023Established 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.
