Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting

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.

The Role of Piezo1 in Regulating Collagen Expression in Orbital Fibroblasts under High Pressure

“…Excessive differentiation of MyoF can lead to abnormal accumulation of collagen, which is regarded as an important risk factor for tissue and organ brosis. Therefore, the activation of broblasts is a key step in the process of tissue brosis, which is regarded as [11][12][13] the main force driving the proliferation and brosis of orbital tissue. Therefore, broblasts have become an important target cell to regulate the process of brosis 14,15 .…”

In Vitro Mechanical Stimulation to Reproduce the Pathological Hallmarks of Human Cardiac Fibrosis on a Beating Chip and Predict The Efficacy of Drugs and Advanced Therapies

“…[20][21][22] Mechano-transduction in cardiac fibrosis has emerged indeed as a fundamental aspect to be considered since mechanical function of CFs actively regulates heart growth, homeostasis, repair and disease. [23] Besides TGF-𝛽, different pathways have been proposed for the cardiac fibrosis process mediated by mechanotransduction: the transcriptional regulation of the Wnt/𝛽-catenin and Hippo pathways are involved in mechanical forces exerted at cell-cell adhesion level, [24] mechanosensitive stimulation activates the RhoA/ROCK pathway [25] and mechanical strain or stress on cardiac tissue, like hypertension, can activate the 𝛽catenin/Wnt signaling pathway. [26] In vitro mechanical stimulation has been also frequently applied to drive CMs maturation.…”