Piezo1 induced apoptosis of type II pneumocytes during ARDS

Liang, Guopeng; Xu, Jing; Cao, Lili; Zeng, Yihua; Chen, Baixu; Yang, Jing; Zhang, Zhongwei; Kang, Yan

doi:10.1186/s12931-019-1083-1

Cited by 36 publications

(29 citation statements)

References 38 publications

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“…2f) 23,24 . This mechanism is further supported by previous studies that show Piezo1 activation leads to the downregulation of Bcl-2 and upregulation of calpain activity 21,39 .…”

Section: Discussionsupporting

confidence: 83%

“…One potential explanation for this shear stress mechanism is the activation of mechanosensitive ion channels (MSCs), specifically the MSC Piezo1. Piezo1 is an MSC that opens in response to mechanical stimuli, such as shear stress and like other MSCs has been previously associated with proapoptotic effects 17–21 . Furthermore, Piezo1 has a small molecule agonist known as Yoda1, meaning Piezo1’s activity can be translated to static conditons 22 .…”

Section: Introductionmentioning

confidence: 99%

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Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability

et al. 2019

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TRAIL specifically induces apoptosis in cancer cells without affecting healthy cells. However, TRAIL’s cancer cytotoxicity was insufficient in clinical trials. Circulatory-shear stress is known to sensitize cancer cells to TRAIL. In this study, we examine the mechanism of this TRAIL sensitization with the goal of translating it to static conditions. GsMTx-4, a Piezo1 inhibitor, was found to reduce shear stress-related TRAIL sensitization, implicating Piezo1 activation as a potential TRAIL-sensitizer. The Piezo1 agonist Yoda1 recreated shear stress-induced TRAIL sensitization under static conditions. A significant increase in apoptosis occurred when PC3, COLO 205, or MDA-MB-231 cells were treated with Yoda1 and TRAIL in combination, but not in Bax-deficient DU145 cells. Calpastatin inhibited apoptosis in Yoda1-TRAIL treated cells, indicating that calpain activation is necessary for apoptosis by Yoda1 and TRAIL. Yoda1 and TRAIL treated PC3 cells showed increased mitochondrial outer membrane permeability (MOMP), mitochondrial depolarization, and activated Bax. This implies that Piezo1 activation sensitizes cancer cells to TRAIL through a calcium influx that activates calpains. The Calpains then induce MOMP by enhancing Bax activation. From these experiments a computational model was developed to simulate apoptosis for cells treated with TRAIL and increased calcium. The computational model elucidated the proapoptotic or antiapoptotic roles of Bax, Bcl-2, XIAP, and other proteins important in the mitochondrial-apoptotic signaling pathway.

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“…2f) 23,24 . This mechanism is further supported by previous studies that show Piezo1 activation leads to the downregulation of Bcl-2 and upregulation of calpain activity 21,39 .…”

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability

et al. 2019

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“…The lung tissue epithelium and the surrounding tissues undergo mechanical stretch generated by air under physiological conditions and mechanical ventilation [ 143 ]. A recent study [ 144 ] demonstrated that the Piezo1 channel was highly expressed in alveolar epithelial type ii cells (AECs), a component of the alveolar epithelium. Over-inflated alveolae caused by mechanical stretch during mechanical ventilation activated the Piezo1 channel, resulting in Ca2 + influx.…”

Section: Function Of Piezo Channelsmentioning

confidence: 99%

“…Over-inflated alveolae caused by mechanical stretch during mechanical ventilation activated the Piezo1 channel, resulting in Ca2 + influx. Subsequently, the elevated intracellular Ca2 + signal led to the apoptosis of AECs, probably through the Bcl-2 pathway [ 144 ] (Fig. 11 B).…”

Section: Function Of Piezo Channelsmentioning

confidence: 99%

Structure, kinetic properties and biological function of mechanosensitive Piezo channels

et al. 2021

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Mechanotransduction couples mechanical stimulation with ion flux, which is critical for normal biological processes involved in neuronal cell development, pain sensation, and red blood cell volume regulation. Although they are key mechanotransducers, mechanosensitive ion channels in mammals have remained difficult to identify. In 2010, Coste and colleagues revealed a novel family of mechanically activated cation channels in eukaryotes, consisting of Piezo1 and Piezo2 channels. These have been proposed as the long-sought-after mechanosensitive cation channels in mammals. Piezo1 and Piezo2 exhibit a unique propeller-shaped architecture and have been implicated in mechanotransduction in various critical processes, including touch sensation, balance, and cardiovascular regulation. Furthermore, several mutations in Piezo channels have been shown to cause multiple hereditary human disorders, such as autosomal recessive congenital lymphatic dysplasia. Notably, mutations that cause dehydrated hereditary xerocytosis alter the rate of Piezo channel inactivation, indicating the critical role of their kinetics in normal physiology. Given the importance of Piezo channels in understanding the mechanotransduction process, this review focuses on their structural details, kinetic properties and potential function as mechanosensors. We also briefly review the hereditary diseases caused by mutations in Piezo genes, which is key for understanding the function of these proteins.

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“…: 1B7G5). The immunohistochemistry of lung was performed as previously reported 51 . In brief, the lung was paraffin embedded and dewaxed, then citrate buffer was used for antigen unmasking.…”

Section: Methodsmentioning

confidence: 99%

Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages

Wang

et al. 2020

Cell Death Dis

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Acute respiratory distress syndrome (ARDS) is common in intensive care units (ICUs), although it is associated with high mortality, no effective pharmacological treatments are currently available. Despite being poorly understood, the role of programmed cell death protein 1 (PD-1) and PD-ligand 1 (PD-L1) axis in ARDS may provide significant insights into the immunosuppressive mechanisms that occur after ARDS. In the present study, we observed that the level of soluble PD-L1 (sPD-L1), a potential activator of the PD-1 pathway, was upregulated in survivors of direct ARDS than in non-survivors. Administration of sPD-L1 in mice with direct ARDS relieved inflammatory lung injury and improved the survival rate, indicating the protective role of sPD-L1 in direct ARDS. Using high-throughput mass cytometry, we found a marked decrease in the number of lung monocyte-derived macrophages (MDMs) with proinflammatory markers, and the protective role of sPD-L1 diminished in ARDS mice with monocyte/macrophage depletion. Furthermore, PD-1 expression increased in the MDMs of patients and mice with direct ARDS. Finally, we showed that sPD-L1 induced MDM apoptosis in patients with direct ARDS. Taken together, our results demonstrated that the engagement of sPD-L1 on PD-1 expressing macrophages resulted in a decrease in pro-inflammatory macrophages and eventually improved direct ARDS. Our study identified a prognostic indicator for patients with direct ARDS and a potential target for therapeutic development in direct ARDS.

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Piezo1 induced apoptosis of type II pneumocytes during ARDS

Cited by 36 publications

References 38 publications

Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability

Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability

Structure, kinetic properties and biological function of mechanosensitive Piezo channels

Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages

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