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Oleg Yarishkin, Tam T T Phuong, Jackson M Baumann, Michael L De Ieso, Felix Vazquez-Chona, Christopher N Rudzitis, Chad Sundberg, Monika Lakk, W Daniel Stamer, David Križaj
KEY POINTS: Trabecular meshwork (TM) is a highly mechanosensitive tissue in the eye that regulates intraocular pressure through the control of aqueous humor drainage. Its dysfunction underlies the progression of glaucoma but neither the mechanisms through which TM cells sense pressure nor their role in aqueous humor outflow are understood at the molecular level. We identified the Piezo1 channel as a key TM transducer of tensile stretch, shear flow and pressure. Its activation resulted in intracellular signals that altered organization of the cytoskeleton and cell-extracellular matrix contacts and modulated the trabecular component of aqueous outflow whereas another channel, TRPV4, mediated a delayed mechanoresponse...
November 23, 2020: Journal of Physiology
#22
Yang Yu, Xiao'an Wu, Sisi Liu, Hongping Zhao, Bo Li, Hucheng Zhao, Xiqiao Feng
Cell migration and invasion are two essential processes during cancer metastasis. Increasing evidence has shown that the Piezo1 channel is involved in mediating cell migration and invasion in some types of cancers. However, the role of Piezo1 in the breast cancer and its underlying mechanisms have not been clarified yet. Here, we show that Piezo1 is high-expressed in breast cancer cell (BCC) lines, despite its complex expression in clinical patient database. Piezo1 knockdown (Piezo1-KD) promotes unconfined BCC migration, but impedes confined cell migration...
November 19, 2020: Acta Biochimica et Biophysica Sinica
#23
R Wadud, A Hannemann, D C Rees, J N Brewin, J S Gibson
Phosphatidylserine (PS) exposure is increased in red cells from sickle cell anaemia (SCA) patients. Externalised PS is prothrombotic and attractive to phagocytes and activated endothelial cells and thus contributes to the anaemic and ischaemic complications of SCA. The mechanism of PS exposure remains uncertain but it can follow increased intracellular Ca2+ concentration ([Ca2+ ]i ). Normally, [Ca2+ ]i is maintained at very low levels but in sickle cells, Ca2+ permeability is increased, especially following deoxygenation and sickling, mediated by a pathway sometimes called Psickle ...
November 18, 2020: Scientific Reports
#24
Yi Sun, Ping Leng, Dawei Li, Huanshen Gao, Zhenghui Li, Chenkai Li, Haining Zhang
Objective: To investigate the effect of small interfering RNA targeting mechanosensitive ion channel protein Piezo1 (Piezo1-siRNA) on abnormal chondrocyte proliferation exposed to mechanical stretch. Methods: Construct and screen effective Piezo1-siRNA sequences and explore an appropriate method to transfect lentiviral vector into chondrocytes exposed to mechanical stretch. Western blot and RT-PCR were used to detect the mRNA and protein expression of Piezo1, Kif18A, and β -tubulin, respectively...
2020: BioMed Research International
#25
Mathilde Filser, Muriel Giansily-Blaizot, Mélanie Grenier, David Monedero Alonso, Guillaume Bouyer, Laurent Peres, Stéphane Egée, Bernard Aral, Fabrice Airaud, Lydie M Da Costa, Veronique Picard, Pierre Cougoul, Marlène Palach, Stephane Bezieau, Céline Garrec, Patricia Aguilar Martinez, Betty Gardie, François Girodon
No abstract text is available yet for this article.
November 12, 2020: Blood
#26
Gretl Hendrickx, Verena Fischer, Astrid Liedert, Simon von Kroge, Melanie Haffner-Luntzer, Laura Brylka, Eva Pawlus, Michaela Schweizer, Timur Yorgan, Anke Baranowsky, Tim Rolvien, Mona Neven, Udo Schumacher, David J Beech, Michael Amling, Anita Ignatius, Thorsten Schinke
The skeleton is a dynamic tissue continuously adapting to mechanical stimuli. Although matrix-embedded osteocytes are considered as the key mechanoresponsive bone cells, all other skeletal cell types are principally exposed to macroenvironmental and microenvironmental mechanical influences that could potentially affect their activities. It was recently reported that Piezo1, one of the two mechanically activated ion channels of the Piezo family, functions as a mechanosensor in osteoblasts and osteocytes. Here we show that Piezo1 additionally plays a critical role in the process of endochondral bone formation...
November 12, 2020: Journal of Bone and Mineral Research
#27
Liguo Zhang, Xiaojie Liu, Lu Gao, Yun Ji, Lulu Wang, Can Zhang, Liping Dai, Jingjing Liu, Zhenyu Ji
The acoustic radiation forces produced by ultrasonic stimulation induce shear stress on objects in the acoustic field. Piezo1, a mechanosensitive ion channel protein that is expressed on the plasma membranes of vertebrate cells, can sense shear stress and transduce it into downstream signaling. In this study, we examined the sensitivity of Piezo1 to ultrasonic stimulation and assessed its downstream biological functions in human umbilical vein endothelial cells (HUVECs). Ultrasonic stimulation using a stimulation power of 0...
November 2020: Biomedicine & Pharmacotherapy
#28
Sally L Baxter, William T Keenan, Argus J Athanas, James A Proudfoot, Linda M Zangwill, Radha Ayyagari, Jeffrey M Liebmann, Christopher A Girkin, Ardem Patapoutian, Robert N Weinreb
Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes...
November 4, 2020: Scientific Reports
#29
Hailin Liu, Wengong Bian, Dongxia Yang, Mingmin Yang, Heguo Luo
AIM: Diabetes is a high-risk factor for neurocognitive dysfunction. Diabetic acute hyperglycaemia accompanied by high osmotic pressure can induce immune cell dysfunction, but its mechanism of action in brain microglia remains unclear. This study aimed to evaluate the role of the mechanically sensitive ion channel piezo1 in the dysfunction of microglia in acute hyperglycaemia. MATERIALS AND METHODS: To construct an in vitro acute hyperglycaemia model using the BV2 microglial cell line, piezo1 in microglia was inhibited by GsMTx4 and siRNA, and the changes in microglial function were further evaluated...
October 27, 2020: Life Sciences
#30
Cristopher V Van Hout, Ioanna Tachmazidou, Joshua D Backman, Joshua D Hoffman, Daren Liu, Ashutosh K Pandey, Claudia Gonzaga-Jauregui, Shareef Khalid, Bin Ye, Nilanjana Banerjee, Alexander H Li, Colm O'Dushlaine, Anthony Marcketta, Jeffrey Staples, Claudia Schurmann, Alicia Hawes, Evan Maxwell, Leland Barnard, Alexander Lopez, John Penn, Lukas Habegger, Andrew L Blumenfeld, Xiaodong Bai, Sean O'Keeffe, Ashish Yadav, Kavita Praveen, Marcus Jones, William J Salerno, Wendy K Chung, Ida Surakka, Cristen J Willer, Kristian Hveem, Joseph B Leader, David J Carey, David H Ledbetter, Lon Cardon, George D Yancopoulos, Aris Economides, Giovanni Coppola, Alan R Shuldiner, Suganthi Balasubramanian, Michael Cantor, Matthew R Nelson, John Whittaker, Jeffrey G Reid, Jonathan Marchini, John D Overton, Robert A Scott, Gonçalo R Abecasis, Laura Yerges-Armstrong, Aris Baras
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1 . Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence...
October 2020: Nature
#31
Zhen Zhao, Berislav V Zlokovic
Like axon guidance, the tuning of vascular tip cells during angiogenesis is an intriguing but puzzling developmental process. A new study in zebrafish (Liu et al., 2020) now demonstrates a critical role of the Piezo1 mechanosensitive ion channel in guiding vascular tip cells in pathfinding.
October 14, 2020: Neuron
#32
Wenjianlong Zhou, Xiangxiang Liu, Jan Willem Maurits van Wijnbergen, Linhao Yuan, Yuan Liu, Chuanbao Zhang, Wang Jia
In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. If and how mechanical cues regulate tumour cell proliferation is currently not fully studied. PIEZO1 has recently been identified as a crucial mechanosensitive cation channel in multiple solid tumours. However, we didn't find any clinical data describing the association between PIEZO1 expression and glioma. To investigate the role of PIEZO1 in gliomas, we analysed PIEZO1 gene expression at the transcriptome level, genomic profiles and the association of PIEZO1 with clinical practice...
September 30, 2020: Scientific Reports
#33
Kana Hasegawa, Shinsuke Fujii, Shinji Matsumoto, Yudai Tajiri, Akira Kikuchi, Tamotsu Kiyoshima
Most cancer cells are exposed to altered extracellular environments, such as an increase in extracellular matrix (ECM) stiffness and soluble signals consisting of growth factors and cytokines. It is therefore conceivable that changes in tumor extracellular environments affect tumor cell behavior. The Hippo pathway reportedly responds to the extracellular environment and regulates the nuclear localization of the transcription co-activator, yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)...
September 28, 2020: Journal of Pathology
#34
Amanda Buyan, Charles D Cox, Jonathan Barnoud, Jinyuan Li, Hannah S M Chan, Boris Martinac, Siewert J Marrink, Ben Corry
Touch, hearing, and blood pressure regulation require mechanically gated ion channels that convert mechanical stimuli into electrical currents. One such channel is Piezo1, which plays a key role in the transduction of mechanical stimuli in humans and is implicated in diseases, such as xerocytosis and lymphatic dysplasia. There is building evidence that suggests Piezo1 can be regulated by the membrane environment, with the activity of the channel determined by the local concentration of lipids, such as cholesterol and phosphoinositides...
September 2, 2020: Biophysical Journal
#35
Pingping Wang, Yinjun Jia, Ting Liu, Yuh-Nung Jan, Wei Zhang
Animal feeding is controlled by external sensory cues and internal metabolic states. Does it also depend on enteric neurons that sense mechanical cues to signal fullness of the digestive tract? Here, we identify a group of piezo-expressing neurons innervating the Drosophila crop (the fly equivalent of the stomach) that monitor crop volume to avoid food overconsumption. These neurons reside in the pars intercerebralis (PI), a neuro-secretory center in the brain involved in homeostatic control, and express insulin-like peptides with well-established roles in regulating food intake and metabolism...
September 8, 2020: Neuron
#36
Francesca Aglialoro, Naomi Hofsink, Menno Hofman, Nicole Brandhorst, Emile van den Akker
The non-selective mechanosensitive ion channel PIEZO1 controls erythrocyte volume homeostasis. Different missense gain-of-function mutations in PIEZO1 gene have been identified that cause Hereditary Xerocytosis (HX), a rare autosomal dominant haemolytic anemia. PIEZO1 expression is not limited to erythrocytes and expression levels are significantly higher in erythroid precursors, hinting to a role in erythropoiesis. During erythropoiesis, interactions between erythroblasts, central macrophages, and extracellular matrix within erythroblastic islands are important...
2020: Frontiers in Physiology
#37
Mingqi Zhang, Xinghuan Ding, Qianqian Zhang, Jian Liu, Yisen Zhang, Ying Zhang, Zhongbin Tian, Wenqiang Li, Wei Zhu, Huibin Kang, Zhongxiao Wang, Xinzhi Wu, Chao Wang, Xinjian Yang, Kun Wang
BACKGROUND: Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants. METHODS: We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease...
August 26, 2020: Journal of Neurointerventional Surgery
#38
Ting-Ting Liu, Xu-Fei Du, Bai-Bing Zhang, Hua-Xing Zi, Yong Yan, Jiang-An Yin, Han Hou, Shan-Ye Gu, Qi Chen, Jiu-Lin Du
During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca2+ activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development. ETC branches display spontaneous local Ca2+ transients, and high- and low-frequency Ca2+ transients cause branch retraction through calpain and branch extension through nitric oxide synthase, respectively...
October 14, 2020: Neuron
#39
Berk Aykut, Ruonan Chen, Jacqueline I Kim, Dongling Wu, Sorin A A Shadaloey, Raquel Abengozar, Pamela Preiss, Anjana Saxena, Smruti Pushalkar, Joshua Leinwand, Brian Diskin, Wei Wang, Gregor Werba, Matthew Berman, Steve Ki Buom Lee, Alireza Khodadadi-Jamayran, Deepak Saxena, William A Coetzee, George Miller
Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor immunity, is not well studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We found signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 with a peptide inhibitor was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells...
August 21, 2020: Science Immunology
#40
Yang Guo, Anna-Lena Merten, Ulrike Schöler, Ze-Yan Yu, Jasmina Cvetkovska, Diane Fatkin, Michael P Feneley, Boris Martinac, Oliver Friedrich
The transformation of electrical signals into mechanical action of the heart underlying blood circulation results in mechanical stimuli during active contraction or passive filling distention, which conversely modulate electrical signals. This feedback mechanism is known as cardiac mechano-electric coupling (MEC). The cardiac MEC involves complex activation of mechanical biosensors initiating short-term and long-term effects through Ca2+ signals in cardiomyocytes in acute and chronic pressure overload scenarios (e...
August 5, 2020: Progress in Biophysics and Molecular Biology
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