Ion channel Piezo1 activation promotes aerobic glycolysis in macrophages

Leng, Shaoqiu; Zhang, Xiaoyu; Wang, Shuwen; Qin, Jing; Liu, Qiang; Liu, Anli; Sheng, Zi; Qi, Feng; Hu, Xiang; Peng, Jun

doi:10.3389/fimmu.2022.976482

Cited by 30 publications

(28 citation statements)

References 67 publications

(49 reference statements)

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“…GsMTx4 suppressed IL-6 production in macrophages as well as DCs in the cLP of DSS-treated mice. These results are in agreement with the reports showing that Piezo1-mediated mechanosensory is crucial for the immune responses in macrophages and DCs [16, 17, 52]. We observed no significant alteration in the percentage of Th1 and Th17 cells in colitis after GsMTx4 treatment under the conditions of our study, which is consistent with the previous study showing that Piezo1 does not influence either proliferation or polarization of Th1 and Th17 cells [18].…”

Section: Discussionsupporting

confidence: 93%

Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis

Liu,

Xia,

et al. 2023

J Innate Immun

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Piezo1, the mechanosensory ion channel, has attracted increasing attention for its essential roles in various inflammatory responses and immune-related diseases. Although most of the key immune cells in inflammatory bowel disease (IBD) have been reported to be regulated by Piezo1, the specific role of Piezo1 in colitis has yet to be intensively studied. The present study investigated the impact of pharmacological inhibition of Piezo1 on dextran sulfate sodium (DSS)-induced colitis, and explored the role of Piezo1 in intestinal immune cells in the context of colitis. We observed upregulated expression of Piezo1 in the colon tissue of mice with DSS-induced colitis. Pharmacological inhibition of Piezo1 by GsMTx4 diminished the severity of colitis. Piezo1 inhibition downregulated the expression of pro-inflammatory mediators Il1b, Il6, and Ptgs2 in colonic tissue, and suppressed the production of IL-6 from macrophages and dendritic cells (DCs), without altering the balance of T helper (Th) cells. In particular, Piezo1 did not affect cell viability, but regulated cell proliferation and production of IL-17A in group 3 innate lymphoid cells (ILC3s), which is dependent on the PI3K-Akt-mTOR signaling pathway. Our findings uncover Piezo1 as an effective regulator in gut inflammation. Targeting Piezo1 could be a promising strategy to modulate intestinal immunity in IBD.

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Section: Discussionsupporting

confidence: 93%

Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis

Liu,

Xia,

et al. 2023

J Innate Immun

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“…Several studies have examined the role of Piezo1 channels in inflammation, with LPS treatment increasing Piezo1 expression in human endothelial cells and Piezo1 knockdown reducing the inflammatory response to LPS ( Liu et al, 2022 ). In a mouse model of acute lung injury, inhibition of Piezo1 reduced inflammation and improved lung function ( Zhang et al, 2021 ), while Piezo1 knockdown decreased the release of proinflammatory cytokines in mouse macrophages ( Leng et al, 2022 ). The effect of inflammation on Piezo1 expression has been investigated, with some studies indicating direct regulation and others suggesting modulation of Piezo1 channels ( Chung et al, 2016 ; Velasco-Estevez et al, 2020b ; Lee et al, 2021 ; Dayawansa et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammation condition sensitizes Piezo1 mechanosensitive channel in mouse cerebellum astrocyte

Ahmed

Jayasi

et al. 2023

Front. Cell. Neurosci.

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Piezo1 mechanosensitive ion channel (MSC) plays a significant role in human physiology. Despite several research on the function and expression of Piezo1 in the nervous system, its electrophysiological properties in neuroinflammatory astrocytes remain unknown. We tested whether astrocytic neuroinflammatory state regulates Piezo1 using electrical recordings, calcium imaging, and wound healing assays on cultured astrocytes. In this study, we determined whether neuroinflammatory condition regulates astrocytic Piezo1 currents in astrocytes. First, we performed electrophysiological recordings on the mouse cerebellum astrocytes (C8-S) under lipopolysaccharide (LPS)-induced neuroinflammatory condition. We found that LPS treatment significantly increased MSC currents in C8-S. The half-maximal pressure of LPS treated MSC currents was left-shifted but the slope sensitivity was not altered by LPS treatment. LPS-induced increase of MSC currents were further augmented by Piezo1 agonist, Yoda1 but were normalized by Piezo1 inhibitor, GsMTx4. Furthermore, silencing Piezo1 in LPS treated C8-S normalized not only MSC currents but also calcium influx and cell migration velocity. Together, our results show that LPS sensitized Piezo1 channel in C8-S astrocytes. These findings will suggest that astrocytic Piezo1 is a determinant of neuroinflammation pathogenesis and may in turn become the foundation of further research into curing several neuronal illnesses and injury related inflammation of neuronal cells.

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“…The Piezo1 pathway has also been implicated in this setting. Deficiency of Piezo1 in monocytes, macrophages and granulocytes made mice less susceptible to DSS-induced colitis, and treatment with Yoda1, an agonist of Piezo1, exacerbated colitis ( Leng et al, 2022 ). The mechanical signals that trigger these pathways in situ are not well understood.…”

Section: Mechanotransduction In Macrophages and Dendritic Cells Durin...mentioning

confidence: 99%

Mechanosensing in macrophages and dendritic cells in steady-state and disease

Lee

Winer

et al. 2022

Front. Cell Dev. Biol.

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Macrophages and dendritic cells are myeloid cells that play critical roles in immune responses. Macrophages help to maintain homeostasis through tissue regeneration and the clearance of dead cells, but also mediate inflammatory processes against invading pathogens. As the most potent antigen-presenting cells, dendritic cells are important in connecting innate to adaptive immune responses via activation of T cells, and inducing tolerance under physiological conditions. While it is known that macrophages and dendritic cells respond to biochemical cues in the microenvironment, the role of extracellular mechanical stimuli is becoming increasingly apparent. Immune cell mechanotransduction is an emerging field, where accumulating evidence suggests a role for extracellular physical cues coming from tissue stiffness in promoting immune cell recruitment, activation, metabolism and inflammatory function. Additionally, many diseases such as pulmonary fibrosis, cardiovascular disease, cancer, and cirrhosis are associated with changes to the tissue biophysical environment. This review will discuss current knowledge about the effects of biophysical cues including matrix stiffness, topography, and mechanical forces on macrophage and dendritic cell behavior under steady-state and pathophysiological conditions. In addition, we will also provide insight on molecular mediators and signaling pathways important in macrophage and dendritic cell mechanotransduction.

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Ion channel Piezo1 activation promotes aerobic glycolysis in macrophages

Cited by 30 publications

References 67 publications

Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis

Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis

Inflammation condition sensitizes Piezo1 mechanosensitive channel in mouse cerebellum astrocyte

Mechanosensing in macrophages and dendritic cells in steady-state and disease

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