Kathrin Diem, Michael Fauler, Giorgio Fois, Andreas Hellmann, Natalie Winokurow, Stefan Schumacher, Christine Kranz, Manfred Frick
Secretion of pulmonary surfactant in the alveoli of the lungs is essential to maintain lung function. Stretching of alveoli during lung inflation is the main trigger for surfactant secretion. Yet, the molecular mechanisms how mechanical distension of alveoli results in surfactant secretion are still elusive. The alveolar epithelium consists of alveolar epithelial type I (ATI) and surfactant secreting type II (ATII) cells. ATI, but not ATII cells, express caveolae, small plasma membrane invaginations that can respond to plasma membrane stresses and serve mechanotransductive roles...
August 3, 2020: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Daniele Zama, Giulia Giulietti, Edoardo Muratore, Immacolata Andolfo, Roberta Russo, Achille Iolascon, Andrea Pession
BACKGROUND: Dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis is a rare, autosomal dominant hemolytic anemia characterized by macrocytosis, presence of stomatocytes and dehydration of red blood cells (RBCs). The dehydration is caused by a defect in cellular cation content. The most frequent expression of the pathology is hemolytic well-compensated anemia with high reticulocyte count, a tendency to macrocytosis, increased mean corpuscular hemoglobin concentration (MCHC) and mild jaundice...
July 23, 2020: Italian Journal of Pediatrics
S Qu, T Hu, O Qiu, Y Su, J Gu, Z Xia
BACKGROUND AND PURPOSE: Previous studies have suggested that increased mortality and disability in patients with brain tumor are associated with peritumoral brain edema. However, the mechanism of peritumoral brain edema in brain tumors is unknown. This study aimed to investigate the effect of Piezo1 overexpression on peritumoral brain edema in glioblastomas. MATERIALS AND METHODS: The Piezo1 expression in cell lines and paired samples was detected by quantitative reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry...
July 16, 2020: AJNR. American Journal of Neuroradiology
Chenghu Zhang, Ting Zhou, Zhipeng Chen, Meng Yan, Bochuan Li, Huizhen Lv, Chunjiong Wang, Song Xiang, Lei Shi, Yi Zhu, Ding Ai
Rationale: Atherosclerosis preferentially occurs at specific sites of the vasculature where endothelial cells (ECs) are exposed to disturbed blood flow. Translocation of integrin α5 to lipid rafts promotes integrin activation and ligation, which is critical for oscillatory shear stress (OSS)-induced EC activation. However, the underlying mechanism of OSS promoted integrin α5 lipid raft translocation has remained largely unknown. Objective: The objective of this study was to specify the mechanotransduction mechanism of OSS-induced integrin α5 translocation and subsequent EC activation...
July 16, 2020: Circulation Research
Ulisse Bocchero, Fabio Falleroni, Simone Mortal, Yunzhen Li, Dan Cojoc, Trevor Lamb, Vincent Torre
Photoreceptors are specialized cells devoted to the transduction of the incoming visual signals. Rods are able also to shed from their tip old disks and to synthesize at the base of the outer segment (OS) new disks. By combining electrophysiology, optical tweezers (OTs), and biochemistry, we investigate mechanosensitivity in the rods of Xenopus laevis, and we show that 1) mechanosensitive channels (MSCs), transient receptor potential canonical 1 (TRPC1), and Piezo1 are present in rod inner segments (ISs); 2) mechanical stimulation-of the order of 10 pN-applied briefly to either the OS or IS evokes calcium transients; 3) inhibition of MSCs decreases the duration of photoresponses to bright flashes; 4) bright flashes of light induce a rapid shortening of the OS; and 5) the genes encoding the TRPC family have an ancient association with the genes encoding families of protein involved in phototransduction...
July 15, 2020: PLoS Biology
Ben Short
JGP study shows that disruption of membrane cholesterol alters the organization and activity of mechanosensitive PIEZO1 channels.
August 3, 2020: Journal of General Physiology
Mauro Siragusa, Alberto Fernando Oliveira Justo, Pedro Felipe Malacarne, Anna Strano, Akshay Buch, Barbara Withers, Kevin G Peters, Ingrid Fleming
AIMS: Receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) dephosphorylates Tie-2 as well as CD31, VE-cadherin and VEGFR2. The latter form a signal transduction complex that mediates the endothelial cell response to shear stress, including the activation of the endothelial nitric oxide (NO) synthase (eNOS). As VE-PTP expression is increased in diabetes, we investigated the consequences of VE-PTP inhibition (using AKB-9778) on blood pressure in diabetic patients and the role of VE-PTP in the regulation of eNOS activity and vascular reactivity...
July 11, 2020: Cardiovascular Research
Erika Sugisawa, Yasunori Takayama, Naoki Takemura, Takeshi Kondo, Shigetsugu Hatakeyama, Yutaro Kumagai, Masataka Sunagawa, Makoto Tominaga, Kenta Maruyama
Gastrointestinal enterochromaffin cells regulate bone and gut homeostasis via serotonin (5-hydroxytryptamine [5-HT]) production. A recent report suggested that gut microbes regulate 5-HT levels; however, the precise underlying molecular mechanisms are unexplored. Here, we reveal that the cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels...
June 29, 2020: Cell
An Song, Lin Lu, Yuxiu Li, Mei Lin, Xingxing Yuan, Xinqi Cheng, Weibo Xia, Ou Wang, Xiaoping Xing
Background: Diabetes is a global disease with rapidly increasing prevalence in the world. Glycated hemoglobin (HbA1c) as an important indicator of diabetes could reflect the average serum glucose level over 120 days. However, when using HbA1c to diagnose diabetes, it is important to consider other factors that may impact HbA1c level including age, race/ethnicity, detection method, and co-morbidities. Here we report a case of diabetes with normal hemoglobin but reduced HbA1c. Case report: A 57-year-old female patient was diagnosed with diabetes by oral glucose tolerance test results...
2020: Frontiers in Endocrinology
Ningfei Liu, Minzhe Gao, Ziyou Yu
OBJECTIVES: To explore the pathology underlying primary lymphedema. METHODS: Twenty-seven patients with unilateral congenital arm lymphedema who visited our clinic from 1 January 2014 to 30 May 2019 were enrolled. The patients' clinical signs, indocyanine green (ICG) lymphography, skin tissue immunohistochemical (IHC) staining, and whole-exome sequencing (WES) of tissue and blood were evaluated. RESULTS: Among the 27 patients, 18 and 9 were diagnosed with stage II and III lymphedema, respectively...
June 26, 2020: Journal of Vascular Surgery. Venous and Lymphatic Disorders
Pietro Ridone, Elvis Pandzic, Massimo Vassalli, Charles D Cox, Alexander Macmillan, Philip A Gottlieb, Boris Martinac
The human mechanosensitive ion channel PIEZO1 is gated by membrane tension and regulates essential biological processes such as vascular development and erythrocyte volume homeostasis. Currently, little is known about PIEZO1 plasma membrane localization and organization. Using a PIEZO1-GFP fusion protein, we investigated whether cholesterol enrichment or depletion by methyl-β-cyclodextrin (MBCD) and disruption of membrane cholesterol organization by dynasore affects PIEZO1-GFP's response to mechanical force...
August 3, 2020: Journal of General Physiology
Saša Svetina
The red blood cell (RBC) membrane contains a mechanosensitive cation channel Piezo1 that is involved in RBC volume homeostasis. In a recent model of the mechanism of its action it was proposed that Piezo1 cation permeability responds to changes of the RBC shape. The aim here is to review in a descriptive manner different previous studies of RBC behavior that formed the basis for this proposal. These studies include the interpretation of RBC and vesicle shapes based on the minimization of membrane bending energy, the analyses of various consequences of compositional and structural features of RBC membrane, in particular of its membrane skeleton and its integral membrane proteins, and the modeling of the establishment of RBC volume...
2020: Frontiers in Physiology
Lennart Kuck, Jason N Peart, Michael J Simmonds
The classic view of the red blood cell (RBC) presents a biologically inert cell, that upon maturation, has limited capacity to alter its physical properties. This view developed largely due to the absence of translational machinery and inability to synthesise or repair proteins in circulating RBC. Recent developments have challenged this perspective, supporting the importance of post-translational modifications, and greater understanding of ion movement in these cells, that each regulate a myriad of cellular properties...
June 24, 2020: American Journal of Physiology. Cell Physiology
Shanqiang Qu, Shuting Li, Zhicheng Hu
Purpose: Previous study reported that Piezo1 was highly expressed in glioma and promoted the proliferation of glioma cells, suggesting that Piezo1 overexpression might contribute to the poor prognosis of patients. Thus, this study aimed to identify whether Piezo1 may become a new prognostic biomarker for glioma patients. Patients and Methods: Firstly, Piezo1 expression of gliomas was analyzed through GEO and Oncomine dataset, and verified by qRT-PCR and immunohistochemistry (IHC) methods...
2020: Cancer Management and Research
Yi Sun, Ping Leng, Mengxiong Song, Dawei Li, Pengcheng Guo, Xipeng Xu, Huanshen Gao, Zhenghui Li, Chenkai Li, Haining Zhang
Studying and understanding the mechanism of inflammation in nucleus pulposus is the key to understand and prevent intervertebral disc degeneration. We propose a model of mechanical sensitive ion channel Piezo1 mediated inflammation of nucleus pulposus cells. Piezo1 can up-regulate the level of interleukin-1β (IL-1β) in nucleus pulposus cells once it is activated. It is suggested that Piezo1 may mediate inflammation by activating Nod-like receptor protein 3 (NLRP3) inflammasome to accelerate the production and maturation of IL-1β...
June 8, 2020: International Immunopharmacology
Silin Liu, Xianmei Pan, Wenbin Cheng, Bo Deng, Yu He, Lei Zhang, Yile Ning, Jing Li
Piezo1, a mechanosensitive Ca2+ -permeable non-selective cationic ion channel protein, is involved in a wide range of biological processes and plays crucial roles in vascular development. However, the pharmacology of this protein is in its infancy. Yoda1, the first specific chemical activator of Piezo1 channels, can activate Piezo1 in absence of mechanical stimulation. Hence, we sought to identify inhibitors of Yoda1 from Traditional Chinese Medicine (TCM). Intracellular Ca2+ measurements were conducted in human umbilical vein endothelial cells (HUVECs), HEK 293T cells overexpressing TRPC5 and TRPM2 channels, as well as in CHO K1 cells overexpressing TRPV4 channels...
2020: Frontiers in Pharmacology
Elisa Darkow, Eva A Rog-Zielinska, Josef Madl, Annette Brandel, Lina Siukstaite, Ramin Omidvar, Peter Kohl, Ursula Ravens, Winfried Römer, Rémi Peyronnet
The healthy heart adapts continuously to a complex set of dynamically changing mechanical conditions. The mechanical environment is altered by, and contributes to, multiple cardiac diseases. Mechanical stimuli are detected and transduced by cellular mechano-sensors, including stretch-activated ion channels (SAC). The precise role of SAC in the heart is unclear, in part because there are few SAC-specific pharmacological modulators. That said, most SAC can be activated by inducers of membrane curvature. The lectin LecA is a virulence factor of Pseudomonas aeruginosa and essential for P...
2020: Frontiers in Physiology
Lei Liu, Shi-Lan Ding, Ying Chen, Qiong-Ling Zhang, Qian Zhang, Zheng-Xiao Sun, Fu-Long Liao, Yun You
The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg~(-1)) group, low-dose and high-dose(50, 150 mg·kg~(-1)) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days...
May 2020: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Xiaofei Bai, Jeff W Bouffard, Avery Lord, Katherine Brugman, Paul W Sternberg, Erin J Cram, Andy Golden
PIEZO1 and PIEZO2 are newly identified mechano-sensitive ion channels that exhibit a preference for calcium in response to mechanical stimuli. In this study, we discovered the vital roles of pezo-1 , the sole PIEZO ortholog in C. elegans, in regulating reproduction. A number of deletion alleles as well as a putative gain-of-function mutant of PEZO-1 caused a severe reduction in brood size. In vivo observations showed that oocytes undergo a variety of transit defects as they enter and exit the spermatheca during ovulation...
June 3, 2020: ELife
Vincenza Caolo, Marjolaine Debant, Naima Endesh, T Simon Futers, Laeticia Lichtenstein, Fiona Bartoli, Gregory Parsonage, Elizabeth Av Jones, David J Beech
Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear stress or a chemical agonist Yoda1 activated a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca2+ -regulated transmembrane sheddase that mediates S2 Notch1 cleavage...
June 2, 2020: ELife
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