Role of Piezo1-mediated mechanotransduction in osteocyte differentiation
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ABSTRACT:
PROVIDER: PRJNA1161617 | ENA |
REPOSITORIES: ENA
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Project description:Mechanical force is a fundamental regulator of bone development and homeostasis. Mechanosensitive osteocytes are the most abundant bone cells that form interconnected dendrites to respond to mechanical stimuli and interact with the bone-forming osteoblasts and the bone-remodeling osteoclasts. However, the molecular mechanisms underlying osteocyte maturation and dendrite formation remain unclear. By generating a Piezo1 "knock-out" osteocyte cell line, we identified a key role of Piezo1-mediated mechanotransduction in osteocyte differentiation. QRT-PCR analysis revealed delayed osteocyte differentiation in the Piezo1 KO cells relative to WT cells. By performing bulk RNA sequencing of WT and Piezo1 KO OCY454 cells at early (D1), intermediate (D14), and late (D28) stages of differentiation allowed for the identification of key signaling pathways in driving normal osteocyte dfiferentiation, as well as those regulated by Piezo1 mechanotransduction.
2024-09-20 | GSE277264 | GEO
Project description:Group-2 innate-lymphoid cells (ILC2s) are critical mediators of the type-2 immune responses in multiple lung pathologies. We show that Piezo1, a mechanosensitive ion channel, plays a key role in regulating ILC2 functions by linking mechanical cues to biochemical signaling pathways. Both murine and human ILC2s strongly express Piezo1, and its activation by Yoda1 selectively enhances IL-13 production through calcium influx, which activates the mTOR-S6K pathway. This pathway leads to translational reprogramming, favoring IL-13 translation. Piezo1-deficient in ILC2s impairs this process, reducing IL-13 levels and resulting in attenuated lung inflammation and fibrosis in mouse models of IL-33- or Alternaria alternata-induced airway inflammation and bleomycin-induced fibrosis. These findings position Piezo1 as a critical mediator of ILC2-driven type-2 immune responses and highlight its potential as a therapeutic target for lung diseases characterized by excessive inflammation. This streamlined understanding of Piezo1 function improves focus on its mechanistic role in lung pathology.
2024-09-30 | GSE278085 | GEO
Project description:Piezo1-mediated Mechanotransduction Shapes ILC2 Translational Activity, Functions, and Lung Pathogenicity
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Project description:Mechanotransduction has been lately recognized as a major regulator of organ homeostasis under a myriad of pathological conditions. The role of Piezo1 in cardiac hypertrophy has never been explored. Here we performed RNA-Seq assay for wild type and Piezo1-Cko mice under sham or TAC surgery.
2024-01-01 | GSE179107 | GEO
Project description:PIEZO1 is a mechanically-activated ion channel that contributes to flow sensing in vascular endothelium. Moreover, deletion of endothelial PIEZO1 was recently found to suppress activation of Notch1 target genes in hepatic microvascular endothelium. Here, because of the liver’s dominant role in lipid regulation, we set out to test the novel hypothesis that endothelial PIEZO1 regulates hepatic lipid homeostasis. We performed bulk RNA sequencing on PIEZO1-deleted mice exposed to chow and high fat diets. Our transcriptomics analysis reveal unexpected relevance to lipid and glucose homeostasis.
2024-06-29 | E-MTAB-9996 | biostudies-arrayexpress
Project description:Neonatal hypoxic-ischemic brain damage (HIBD) is initiated by perinatal asphyxia, leading to brain injury triggered by reduced blood and oxygen flow, resulting in neurological impairments such as cerebral palsy, epilepsy, cognitive deficits, and behavioral disorders.Recent insights collectively suggest the important roles of lysyl oxidase (LOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms in HIBD remain elusive.In this study, we found through the study of HIBD rat models and the oxygen-glucose deprivation/re-oxygenation (OGD/R) cell models that LOX significantly increased after HIBD or OGD/R. RNA seq results showed a significant increase in piezo1 after primary neuron OGD/R, and iron death data was also enriched. Moreover, inhibiting LOX or piezo1 can rescue neuronal ferroptosis and further improve cognitive function in rats. In addition, we also found that traumatic acid can inhibit the enzyme activity of LOX and improve a series of pathological features of neuronal damage caused by increased LOX.
2024-09-25 | GSE270560 | GEO
Project description:It is generally believed that bone micro-fractures, associated with osteocyte death, lead to osteoclast recruitment and thereupon to removal and replacement of damaged bone. However, the underlying mechanism is still incompletely defined. In this study we hypothesized that the pattern recognition receptor macrophage-inducible C-type lectin (Mincle) is expressed in osteoclasts and is responsible for the recognition of osteocyte death. To understand the mechanistic role of Mincle in osteoclasts, we performed in-depth analysis of the effect of Mincle deficiency on the genomic transcriptional network of osteoclasts. Whole transcriptome RNA sequencing (RNAseq) was performed on osteoclasts stimulated with necrotic osteocyte supernatant compared to control osteoclasts (stimulated with viable osteocyte supernatant), derived from either wildtype or Mincle knockout mice.
2020-12-05 | GSE151049 | GEO
Project description:PIEZO1 is a mechanosensitive ion channel involved in the regulation of a diverse range of physiological responses. We examined the role of the mechanosensor ion channel PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells. PIEZO1 expression is elevated in β-cells from human donors with type-2 diabetes (T2D) and a rodent T2D model (db/db 48 mouse). Silencing of Piezo1 inhibits glucose-induced Ca2+ signaling and insulin secretion. PIEZO1 translocates from the cytosol and plasmalemma into the nucleus in cells cultured at high glucose, experimental conditions emulating diabetes. The translocation of PIEZO1 into the nucleus in response to hyperglycemia suggests that PIEZO1 might be involved in transcriptional control in addition to serving as a mechanosensor in the plasma membrane. To address this, we performed mRNA sequencing in INS-1 832/13 cells to determine which genes are regulated by Piezo channels. Overall, we found 3292, 1656, and 1920 genes were significantly differentially expressed after silencing Piezo1, Piezo2, or both genes (adj.p-value < 0.05). Among these, the expression of the gene encoding cocaine- and amphetamine-regulated transcript (Cartpt) was increased >15-fold. We confirmed this effect by qPCR, which indicated a corresponding stimulation of expression. In insulin-secreting INS-1 832/13 cells, Cart has been reported to influence the expression and release of insulin. Thus, the impact of PIEZO1 on β-cell function may not be limited to electrical excitability but these changes are likely to operate on a slower timescale than the acute/electrical effects.
2022-05-20 | GSE197449 | GEO
Project description:Tendon tissue growth is promoted by mechanical stimulation, but the mechanism is not well understood. Piezo1, a mechanical stress-responsive channel receptor, is expressed in tendon cells, and the fact that tendon tissue growth was accelerated in Piezo1 gain of function mice suggests that Piezo1 plays an important role in tendon tissue growth. RNA-seq of tendon tissues from these mice showed increased expression of tendon-related genes and decreased expression of muscle-related genes, suggesting that Piezo1 may play a role in maintaining and enhancing the properties of tendon cells.
2021-09-20 | GSE169261 | GEO
Project description:Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent provocative findings describe a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observed that fecal extracts and ssRNA stimulate calcium influx in certain cell lines, this response was independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA showed similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.
2022-11-16 | GSE213903 | GEO