Abstract
Fibrosis, a pathologic process featured by the excessive deposition of connective tissue components, can affect virtually every organ and has no satisfactory therapy yet. Fibrotic diseases are often associated with organ dysfunction which leads to high morbidity and mortality. Biomechanical stmuli and the corresponding cellular response havebeen identified in fibrogenesis, as the fibrotic remodeling could be seen as the incapacity to reestablish mechanical homeostasis: along with extracellular matrix accumulating, the physical property became more “stiff” and could in turn induce fibrosis. In this review, we provide a comprehensive overview of mechanoregulation in fibrosis, from initialing cellular mechanosensing to intracellular mechanotransduction and processing, and ends up in mechanoeffecting. Our contents are not limited to the cellular mechanism, but further expand to the disorders involved and current clinical trials, providing an insight into the disease and hopefully inspiring new approaches for the treatment of tissue fibrosis.
Highlights
Fibrosis is a process featuring excessive deposition of extracellular matrix (ECM) proteins, which leads to scarring and thickening of the affected tissue (Rockey et al, 2015)
We provide a comprehensive overview of mechanoregulation in fibrosis, from initialing cellular mechanosensing to intracellular mechanotransduction and processing, and ends up in mechanoeffecting
A study found that calciumsensing receptors (CaSR) expression in zebrafish lateral-line hair cells regulates mechanotransducer-channel-mediated calcium entry (Lin et al, 2018), suggesting that CaSR is involved in mechanotransduction and could be a potential therapeutic target
Summary
Fibrosis is a process featuring excessive deposition of extracellular matrix (ECM) proteins, which leads to scarring and thickening of the affected tissue (Rockey et al, 2015). Cells can sense changes in the physical environment, and subsequently transduce extracellular mechanical signals into intracellular biochemical reactions and gene expression regulation (Saucerman et al, 2019). When the mechanical homeostasis is disrupted, fibroblast activation becomes uncontrolled and results in amplified ECM generation (Tschumperlin et al, 2018). The progressive deposition of ECM results in tissue stiffening, leading to a self-amplifying loop of fibroblast activation, and providing a greater mechanical context for fibrogenesis. Understanding how biophysical parameters of the mechanical environment regulate cell behavior is of great importance in fibrosis. We believe that a deeper understanding of biomechanics could provide new insights into mechanoregulation in fibrotic tissue remodeling, and help us identify novel therapies
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