TRPV4 promotes acoustic wave-mediated BBB opening via Ca2+/PKC-δ pathway

Liao, Wei-Hao; Hsiao, Ming‐Yen; Kung, Yi; Liu, Hao-Li; Béra, Jean‐Christophe; Inserra, Claude; Chen, Wen-Shiang

doi:10.1016/j.jare.2020.06.012

Cited by 25 publications

(15 citation statements)

References 72 publications

(111 reference statements)

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“…Possibly actin cytoskeleton passed the force to trigger the ER Ca 2+ signals ( Kim et al, 2015 ), which is also suggested from our data ( Figures 5A–E ). Ca 2+ signals can further activate PKC to induce Ras-Raf-MEK-ERK pathway ( Liao et al, 2020 ; Yan et al, 2020 ), and our data showed that inhibition of Ras truly blocked the mechanical activation of ERK ( Figures 5D,E ). These data indicate that actin cytoskeleton belongs to the mechanosensing component for ERK activation.…”

Section: Discussionmentioning

confidence: 56%

FRET Visualization of Cyclic Stretch-Activated ERK via Calcium Channels Mechanosensation While Not Integrin β1 in Airway Smooth Muscle Cells

Fang

Guo

et al. 2022

Front. Cell Dev. Biol.

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Mechanical stretch is one type of common physiological activities such as during heart beating, lung breathing, blood flow through the vessels, and physical exercise. The mechanical stimulations regulate cellular functions and maintain body homeostasis. It still remains to further characterize the mechanical-biomechanical coupling mechanism. Here we applied fluorescence resonance energy transfer (FRET) technology to visualize ERK activity in airway smooth muscle (ASM) cells under cyclic stretch stimulation in airway smooth muscle (ASM) cells, and studied the mechanosensing pathway. FRET measurements showed apparent ERK activation by mechanical stretch, which was abolished by ERK inhibitor PD98059 pretreatment. Inhibition of extracellular Ca2+ influx reduced ERK activation, and selective inhibition of inositol 1,4,5-trisphosphate receptor (IP3R) Ca2+ channel or SERCA Ca2+ pump on endoplasmic reticulum (ER) blocked the activation. Chemical inhibition of the L-type or store-operated Ca2+ channels on plasma membrane, or inhibition of integrin β1 with siRNA had little effect on ERK activation. Disruption of actin cytoskeleton but not microtubule one inhibited the stretch-induced ERK activation. Furthermore, the ER IP3R-dependent ERK activation was not dependent on phospholipase C-IP3 signal, indicating possibly more mechanical mechanism for IP3R activation. It is concluded from our study that the mechanical stretch activated intracellular ERK signal in ASM cells through membrane Ca2+ channels mechanosensation but not integrin β1, which was mediated by actin cytoskeleton.

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Section: Discussionmentioning

confidence: 56%

FRET Visualization of Cyclic Stretch-Activated ERK via Calcium Channels Mechanosensation While Not Integrin β1 in Airway Smooth Muscle Cells

Fang

Guo

et al. 2022

Front. Cell Dev. Biol.

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“…Our previous studies proved that SW effectively induces BBB opening without UCAs or microbubbles ( 26 , 34 ). In addition, the current research demonstrates that SW effectively opened the BBB without causing tissue damage ( Figures 2A–C ).…”

Section: Resultsmentioning

confidence: 98%

“…The molecular mechanism of using SW to open the blood-brain barrier is not fully understood. In addition to the aforementioned computational studies, our previous research indicated that SW can activate TRPV4 channels on vascular endothelial cells membrane to promote C 2+ influx into endothelial cells and then activate the PKCdelta signaling pathway, which finally leads to the disruption of tight junctions ( 34 ). Adding TRPV4 agonists was shown to reduce the necessary SW intensity, which may help to reduce tissue damage caused by excessive mechanical force of SW in future applications.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma

et al. 2021

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BackgroundGlioblastoma multiforme (GBM) is currently the most devastating brain tumor globally and produces a high mortality rate. GBM is also challenging to eradicate using surgery due to its invasive characteristics. Moreover, the blood-brain barrier (BBB) increases the difficulty of transporting most therapeutic drugs to tumor sites. The use of transcranial focused ultrasound (FUS) has recently been investigated for opening the BBB to facilitate drug delivery. A special form of FUS, the shockwave (SW), has also been shown to open BBB efficiently. SW has several advantages including no heating effect, less reactive oxygen species production, good transcranial ability, and no need to supply microbubbles.MethodsWe employed a commercial SW device, which is a common tool used for musculoskeletal disorders, to improve doxorubicin delivery across the BBB and evaluated its therapeutic efficacy on GBM rat models. SW emits relatively short but stronger mechanical pulses comparing with FUS.ResultsThe results demonstrated that doxorubicin combined with SW treatment substantially inhibited tumor growth and prolonged overall survival.ConclusionsThe present study shows the non-invasive transcranial SW may have potential for the treatment of GBM in future clinical setting.

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“…The current investigation on US neuromodulation mechanism relies in two aspects, namely, physical mechanism and neuronal mechanism. In terms of the neuronal mechanism, many studies have investigated the role of various mechanosensitive ion channels in US stimulation [46][47][48][49][50]; however, their conclusions are inconsistent and inconclusive. A more comprehensive study is still required to uncover the neuronal mechanism of US stimulation of the retina.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Ultrasound Retinal Stimulation for Vision Restoration at High Spatiotemporal Resolution

Qian

Thomas

et al. 2022

BME Front

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Objective . Retinal degeneration involving progressive deterioration and loss of function of photoreceptors is a major cause of permanent vision loss worldwide. Strategies to treat these incurable conditions incorporate retinal prostheses via electrically stimulating surviving retinal neurons with implanted devices in the eye, optogenetic therapy, and sonogenetic therapy. Existing challenges of these strategies include invasive manner, complex implantation surgeries, and risky gene therapy. Methods and Results . Here, we show that direct ultrasound stimulation on the retina can evoke neuron activities from the visual centers including the superior colliculus and the primary visual cortex (V1), in either normal-sighted or retinal degenerated blind rats in vivo . The neuron activities induced by the customized spherically focused 3.1 MHz ultrasound transducer have shown both good spatial resolution of 250 μ m and temporal resolution of 5 Hz in the rat visual centers. An additional customized 4.4 MHz helical transducer was further implemented to generate a static stimulation pattern of letter forms. Conclusion . Our findings demonstrate that ultrasound stimulation of the retina in vivo is a safe and effective approach with high spatiotemporal resolution, indicating a promising future of ultrasound stimulation as a novel and noninvasive visual prosthesis for translational applications in blind patients.

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TRPV4 promotes acoustic wave-mediated BBB opening via Ca2+/PKC-δ pathway

Abstract: Graphical abstract

Cited by 25 publications

References 72 publications

FRET Visualization of Cyclic Stretch-Activated ERK via Calcium Channels Mechanosensation While Not Integrin β1 in Airway Smooth Muscle Cells

FRET Visualization of Cyclic Stretch-Activated ERK via Calcium Channels Mechanosensation While Not Integrin β1 in Airway Smooth Muscle Cells

Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma

Noninvasive Ultrasound Retinal Stimulation for Vision Restoration at High Spatiotemporal Resolution

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