Piezo1

Macrophages (MΦ) play pivotal roles in tissue homeostasis and repair. Their mechanical environment has been identified as a key modulator of various cell functions, and MΦ mechanosensitivity is likely to be critical - in particular in a rhythmically contracting organ such as the heart. Cultured MΦ, differentiated in vitro from bone marrow (MΦBM ), form a popular research model. This study explores the activity of mechanosensitive ion channels (MSC) in murine MΦBM and compares it to MSC activity in MΦ enzymatically isolated from cardiac tissue (tissue-resident MΦ; MΦTR )...

Ophthalmic diseases affect many people, causing partial or total loss of vision and a reduced quality of life. The anterior segment of the eye accounts for nearly half of all visual impairment that can lead to blindness. Therefore, there is a growing demand for ocular research and regenerative medicine that specifically targets the anterior segment to improve vision quality. This study aims to generate a microfluidic platform for investigating the formation of the anterior segment of the eye derived from human induced pluripotent stem cells (hiPSC) under various spatial-mechanoresponsive conditions...

BACKGROUND: Cerebral infarction often results in post-stroke cognitive impairment, which impairs the quality of life and causes long-term disability. Astrocytes, the most abundant glial cells in the central nervous system, have a crucial role in cerebral ischemia and neuroinflammation. We explored the possible advantages of interleukin-6 (IL-6), a powerful pro-inflammatory cytokine produced by astrocytes, for post-stroke cognitive function. METHODS: Mendelian randomization was applied to analyze the GWAS database of stroke patients, obtaining a causal relationship between IL-6 and stroke...

Differences in shape can be a distinguishing feature between different cell types, but the shape of a cell can also be dynamic. Changes in cell shape are critical when cancer cells escape from the primary tumor and undergo major morphological changes that allow them to squeeze between endothelial cells, enter the vasculature, and metastasize to other areas of the body. A shift from rounded to spindly cellular geometry is a consequence of epithelial-mesenchymal plasticity, which is also associated with changes in gene expression, increased invasiveness, and therapeutic resistance...

BACKGROUND: Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. MATERIALS AND METHODS: Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale...

Mechanosensitive ion channels are widely distributed in the heart, lung, bladder and other tissues, and plays an important role in exercise-induced cardiovascular function promotion. By reviewing the PubMed databases, the results were summarized using the terms "Exercise/Sport", "Piezo1", "Transient receptor potential (TRP)" and "Cardiovascular" as the keywords, 124-related papers screened were sorted and reviewed. The results showed that: (1) Piezo1 and TRP channels play an important role in regulating blood pressure and the development of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cardiac fibrosis; (2) Exercise promotes cardiac health, inhibits the development of pathological heart to heart failure, regulating the changes in the characterization of Piezo1 and TRP channels; (3) Piezo1 activates downstream signaling pathways with very broad pathways, such as AKT/eNOS, NF-κB, p38MAPK and HIPPO-YAP signaling pathways...

AIMS: Excessive occlusal force with periodontitis leads to rapid alveolar bone resorption. However, the molecular mechanism by which inflammation and mechanical stress cause bone resorption remains unclear. We examined the role of Piezo1, a mechanosensitive ion channel expressed on osteoblasts, in the changes in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio in mouse MC3T3-E1 osteoblast-like cells under Porphyromonas gingivalis lipopolysaccharide (P...

Natural bone tissue features a complex mechanical environment, with cells responding to diverse mechanical stimuli, including fluid shear stress (FSS) and hydrostatic pressure (HP). However, current in vitro experiments commonly employ a singular mechanical stimulus to simulate the mechanical environment in vivo. The understanding of the combined effects and mechanisms of multiple mechanical stimuli remains limited. Hence, this study constructed a mechanical stimulation device capable of simultaneously applying FSS and HP to cells...

Piezo1 and Piezo2 are novel mechanosensory ion channels that transduce mechanical stimuli from the environment into intracellular biochemical signals in various tissues and organ systems. Here, we showed that Piezo1 and Piezo2 displayed a robust expression during jawbone development. Deletion of Piezo1 in neural crest cells caused jawbone malformations in a small but significant number of mice. We further demonstrated that disruption of Piezo1 and Piezo2 in neural crest cells caused more striking defects in jawbone development than any single knockout, suggesting essential but partially redundant roles of Piezo1 and Piezo2...

The Piezo1 mechanosensitive ion channel is abundant on several elements of the central nervous system including astrocytes. It has been already demonstrated that activation of these channels is able to elicit calcium waves on astrocytes, which contributes to the release of gliotransmitters. Astrocyte- and N-methyl-D-aspartate (NMDA) receptor-dependent slow inward currents (SICs) are hallmarks of astrocyte-neuron communication. These currents are triggered by glutamate released as gliotransmitter, which in turn activates neuronal NMDA receptors responsible for this inward current having slower kinetics than any synaptic events...

This work introduces NeoMag, a system designed to enhance cell mechanics assays in substrate deformation studies. NeoMag uses multidomain magneto-active materials to mechanically actuate the substrate, transmitting reversible mechanical cues to cells. The system boasts full flexibility in alternating loading substrate deformation modes, seamlessly adapting to both upright and inverted microscopes. The multidomain substrates facilitate mechanobiology assays on 2D and 3D cultures. The integration of the system with nanoindenters allows for precise evaluation of cellular mechanical properties under varying substrate deformation modes...

OBJECTIVES: Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. MATERIALS AND METHODS: Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device...

TRAAK, TREK-1, and TREK-2 are mechanosensitive two-pore domain K+ (K2P) channels that contribute to action potential propagation, sensory transduction, and muscle contraction. While structural and functional studies have led to models that explain their mechanosensitivity, we lack a quantitative understanding of channel activation by membrane tension. Here, we define the tension response of mechanosensitive K2Ps using patch-clamp recording and imaging. All are low-threshold mechanosensitive channels (T10%/50% 0...

All animal cells control their volume through a complex set of mechanisms, both to counteract osmotic perturbations of the environment and to enable numerous vital biological processes, such as proliferation, apoptosis, and migration. The ability of cells to adjust their volume depends on the activity of ion channels and transporters which, by moving K+ , Na+ , and Cl- ions across the plasma membrane, generate the osmotic gradient that drives water in and out of the cell. In 2010, Patapoutian's group identified a small family of evolutionarily conserved, Ca2+ -permeable mechanosensitive channels, Piezo1 and Piezo2, as essential components of the mechanically activated current that mediates mechanotransduction in vertebrates...

BACKGROUND: MiR-107 is reduced in sepsis and associated with inflammation regulation. Dietary supplementation with polyunsaturated fatty acids (ω3-PUFA) can increase the expression of miR-107; this study investigated whether the ω3-PUFA can effectively inhibit neuroinflammation and improve cognitive function by regulating miR-107 in the brain. METHODS: The LPS-induced mouse model of neuroinflammation and the BV2 cell inflammatory model were used to evaluate the effects of ω3-PUFA on miR-107 expression and inflammation...

The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive...

INTRODUCTION: Intestinal barrier dysfunction is a pivotal factor in sepsis progression. The mechanosensitive ion channel Piezo1 is associated with barrier function; however, its role in sepsis-induced intestinal barrier dysfunction remains poorly understood. METHODS: The application of cecal ligation and puncture (CLP) modeling was performed on both mice of the wild-type (WT) variety and those with Villin-Piezo1flox/flox genetic makeup to assess the barrier function using in vivo FITC-dextran permeability measurements and immunofluorescence microscopy analysis of tight junctions (TJs) and apoptosis levels...

INTRODUCTION: Erythrocytosis is attributed to various clinical and molecular factors. Many cases of JAK2-unmutated erythrocytosis remain undiagnosed. We investigated the characteristics and causes of JAK2-unmutated erythrocytosis. METHODS: We assessed the clinical and laboratory results of patients with erythrocytosis without JAK2 mutations and performed targeted next-generation sequencing (NGS) panels for somatic and germline mutations. RESULTS: In total, 117 patients with JAK2-unmutated erythrocytosis were included...

Neural crest cells (NCC) comprise a heterogeneous population of cells with variable potency, that contribute to nearly every tissue and organ system throughout the body. Considered unique to vertebrates, NCC are transiently generated within the dorsolateral region of the neural plate or neural tube, during neurulation. Their delamination and migration are crucial events in embryo development as the differentiation of NCC is heavily influenced by their final resting locations. Previous work in avian and aquatic species has shown that NCC delaminate via an epithelial-mesenchymal transition (EMT), which transforms these stem and progenitor cells from static polarized epithelial cells into migratory mesenchymal cells with fluid front and back polarity...

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states...