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https://www.readbyqxmd.com/read/28324742/epithelial-homeostasis-a-piezo-of-the-puzzle
#1
Eugenia Piddini
A recent study shows that, upon stretching or wounding, epithelia display a fast proliferative response that allows for re-establishment of optimal cell density or sealing of the wound. This increased proliferation is induced by the stretch-activated channel Piezo1 and involves calcium-triggered ERK signalling.
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28199303/mechanical-stretch-triggers-rapid-epithelial-cell-division-through-piezo1
#2
S A Gudipaty, J Lindblom, P D Loftus, M J Redd, K Edes, C F Davey, V Krishnegowda, J Rosenblatt
Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die. However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state...
March 2, 2017: Nature
https://www.readbyqxmd.com/read/28164706/mechanical-stimulation-of-piezo1-receptors-depends-on-extracellular-matrix-proteins-and-directionality-of-force
#3
Benjamin M Gaub, Daniel J Müller
Piezo receptors convert mechanical forces into electrical signals. In mammals, they play important roles in basic physiological functions including proprioception, sensation of touch, and vascular development. However, basic receptor properties like the gating mechanism, the interaction with extracellular matrix (ECM) proteins, and the response to mechanical stimulation, remain poorly understood. Here, we establish an atomic force microscopy (AFM)-based assay to mechanically stimulate Piezo1 receptors in living animal cells, while monitoring receptor activation in real-time using functional calcium imaging...
March 8, 2017: Nano Letters
https://www.readbyqxmd.com/read/28135189/direct-measurement-of-trpv4-and-piezo1-activity-reveals-multiple-mechanotransduction-pathways-in-chondrocytes
#4
M Rocio Servin-Vences, Mirko Moroni, Gary R Lewin, Kate Poole
The joints of mammals are lined with cartilage, comprised of individual chondrocytes embedded in a specialized extracellular matrix. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis. It has been proposed that mechanically gated ion channels are of functional importance in chondrocyte mechanotransduction; however, direct evidence of mechanical current activation in these cells has been lacking. We have used high-speed pressure clamp and elastomeric pillar arrays to apply distinct mechanical stimuli to primary murine chondrocytes, stretch of the membrane and deflection of cell-substrate contacts points, respectively...
January 30, 2017: ELife
https://www.readbyqxmd.com/read/28121068/hemoglobin-c-trait-accentuates-erythrocyte-dehydration-in-hereditary-xerocytosis
#5
Elizabeth Yang, Erin B Voelkel, Kimberly Lezon-Geyda, Vincent P Schulz, Patrick G Gallagher
A 17-year-old male presented with acute hemolysis with stomatocytosis, elevated mean corpuscular hemoglobin concentration (MCHC), and osmotic gradient ektacytometry consistent with marked erythrocyte dehydration. Erythrocytes from both parents also demonstrated evidence of dehydration with elevated MCHC and abnormal ektacytometry, but neither to the degree of the patient. Genetic studies revealed the patient had hereditary xerocytosis (HX) due to a novel PIEZO1 mutation inherited from his mother and hemoglobin C (HbC) trait inherited from his father...
January 25, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28076814/gsmtx4-mechanism-of-inhibiting-mechanosensitive-ion-channels
#6
Radhakrishnan Gnanasambandam, Chiranjib Ghatak, Anthony Yasmann, Kazuhisa Nishizawa, Frederick Sachs, Alexey S Ladokhin, Sergei I Sukharev, Thomas M Suchyna
GsMTx4 is a spider venom peptide that inhibits cationic mechanosensitive channels (MSCs). It has six lysine residues that have been proposed to affect membrane binding. We synthesized six analogs with single lysine-to-glutamate substitutions and tested them against Piezo1 channels in outside-out patches and independently measured lipid binding. Four analogs had ∼20% lower efficacy than the wild-type (WT) peptide. The equilibrium constants calculated from the rates of inhibition and washout did not correlate with the changes in inhibition...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28060940/clock-genes-regulate-the-circadian-expression-of-piezo1-trpv4-connexin26-and-vnut-in-an-ex-vivo-mouse-bladder-mucosa
#7
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Karl-Erik Andersson, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
OBJECTIVES: ClockΔ19/Δ19 mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from ClockΔ19/Δ19 mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular nucleotide transporter (VNUT) and Connexin26(Cx26), in addition to clock genes. MATERIALS AND METHODS: Eight- to twelve-week-old male C57BL/6 mice (WT) and age- and sex-matched C57BL/6 ClockΔ19/Δ19 mice, which were bred under 12-h light/dark conditions for 2 weeks, were used...
2017: PloS One
https://www.readbyqxmd.com/read/28044050/piezo2-a-candidate-biomarker-for-visceral-hypersensitivity-in-irritable-bowel-syndrome
#8
Tao Bai, Ying Li, Jing Xia, Yudong Jiang, Lei Zhang, Huan Wang, Wei Qian, Jun Song, Xiaohua Hou
Background/Aim: Currently, there exists no biomarker for visceral hypersensitivity in Irritable Bowel Syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold...
January 2, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/27829145/piezo1-channels-are-inherently-mechanosensitive
#9
Ruhma Syeda, Maria N Florendo, Charles D Cox, Jennifer M Kefauver, Jose S Santos, Boris Martinac, Ardem Patapoutian
The conversion of mechanical force to chemical signals is critical for many biological processes, including the senses of touch, pain, and hearing. Mechanosensitive ion channels play a key role in sensing the mechanical stimuli experienced by various cell types and are present in organisms from bacteria to mammals. Bacterial mechanosensitive channels are characterized thoroughly, but less is known about their counterparts in vertebrates. Piezos have been recently established as ion channels required for mechanotransduction in disparate cell types in vitro and in vivo...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27797339/endothelial-cation-channel-piezo1-controls-blood-pressure-by-mediating-flow-induced-atp-release
#10
ShengPeng Wang, Ramesh Chennupati, Harmandeep Kaur, Andras Iring, Nina Wettschureck, Stefan Offermanns
Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress-induced stimulation of NO formation. However, the mechanism by which fluid shear stress initiates these processes is unclear. Here, we have shown that the endothelial mechanosensitive cation channel PIEZO1 is required for flow-induced ATP release and subsequent P2Y2/Gq/G11-mediated activation of downstream signaling that results in phosphorylation and activation of AKT and endothelial NOS...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27779758/trpv4-participates-in-pressure-induced-inhibition-of-renin-secretion-by-juxtaglomerular-cells
#11
François Seghers, Xavier Yerna, Nadège Zanou, Olivier Devuyst, Rudi Vennekens, Bernd Nilius, Philippe Gailly
KEY POINTS: Increase in blood pressure in the renal afferent arteriole is known to induce an increase in cytosolic calcium concentration ([Ca(2+) ]i ) of juxtaglomerular (JG) cells and to result in a decreased secretion of renin. Mechanical stimulation of As4.1 JG cells induces an increase in [Ca(2+) ]i that is inhibited by HC067047 and RN1734, two inhibitors of TRPV4, or by siRNA-mediated repression of TRPV4. Inhibition of TRPV4 impairs pressure-induced decrease in renin secretion. Compared to wild-type mice, Trpv4(-/-) mice present increased resting plasma levels of renin and aldosterone and present a significantly altered pressure-renin relationship...
December 15, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27756835/new-insights-on-hereditary-erythrocyte-membrane-defects
#12
REVIEW
Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances...
November 2016: Haematologica
https://www.readbyqxmd.com/read/27756599/piezo1-expression-increases-in-rat-bladder-after-partial-bladder-outlet-obstruction
#13
Mai Michishita, Kazuo Yano, Ken-Ichi Tomita, Osamu Matsuzaki, Ken-Ichi Kasahara
AIMS: For patients with benign prostatic hyperplasia (BPH), storage symptoms due to bladder dysfunction are bothersome, and that mechanism elucidation is needed. Piezo1, a mechanically activated ion channel, is believed to play a role in sensing bladder distension. To investigate the involvement of Piezo1 in bladder dysfunction, we examined the expression and distribution of Piezo1 and neurofilament (NF-L) to understand pathological alterations in rat bladders with partial bladder outlet obstruction (pBOO), an animal model of BPH...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27743844/touch-tension-and-transduction-the-function-and-regulation-of-piezo-ion-channels
#14
REVIEW
Jason Wu, Amanda H Lewis, Jörg Grandl
In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel...
January 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27694883/localized-force-application-reveals-mechanically-sensitive-domains-of-piezo1
#15
Jason Wu, Raman Goyal, Jörg Grandl
Piezos are mechanically activated ion channels that function as sensors of touch and pressure in various cell types. However, the precise mechanism and structures mediating mechanical activation and subsequent inactivation have not yet been identified. Here we use magnetic nanoparticles as localized transducers of mechanical force in combination with pressure-clamp electrophysiology to identify mechanically sensitive domains important for activation and inactivation.
October 3, 2016: Nature Communications
https://www.readbyqxmd.com/read/27643431/mechanosensing-is-critical-for-axon-growth-in-the-developing-brain
#16
David E Koser, Amelia J Thompson, Sarah K Foster, Asha Dwivedy, Eva K Pillai, Graham K Sheridan, Hanno Svoboda, Matheus Viana, Luciano da F Costa, Jochen Guck, Christine E Holt, Kristian Franze
During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain...
December 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27562045/-mechanism-of-the-piezo1-protein-induced-apoptosis-of-the-chondrocytes-through-the-mapk-erk1-2-signal-pathway
#17
X F Li, Z Zhang, X D Li, T B Wang, H N Zhang
OBJECTIVE: To invstigate the mechanism of new mechanically-activated cation channel protein (Piezo1) can cause the apoptosis of the human chondrocytes under compressive loading, using a Flexercell unit by activating classical Mitogen-activated protein kinase (MAPK) signal pathyway(ERK1/2). METHODS: Primary human chondrocytes were isolated, cultured, and then subjected to the static compressive loading for 0, 2, 12, 24, 48 h, respectively.The expressions of Piezo1 and the ERK1/2 were assessed by reverse transcription-polymerase chain reaction(PT-PCR), as well as the apoptosis gene B cell lymphoma/leukemia-2(Bcl-2) Bel-associated X protein(Bax)...
August 16, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27515482/mir-103a-targeting-piezo1-is-involved-in-acute-myocardial-infarction-through-regulating-endothelium-function
#18
Lingzhi Huang, Lezhi Li, Xiaofang Chen, Huiling Zhang, Zeya Shi
BACKGROUND: Acute myocardial infarction (AMI) is commonly known as the heart attack. The molecular events involved in the development of AMI remain unclear. This study was to investigate the expression of miR-103a in patients with high blood pressure (HBP) and AMI patients with and without HBP, as well as its effect on endothelial cell functions. METHODS: MiR-103a expression in plasma and peripheral blood mononuclear cells was measured by real-time polymerase chain reaction (PCR)...
August 12, 2016: Cardiology Journal
https://www.readbyqxmd.com/read/27353637/advances-in-understanding-the-pathogenesis-of-the-red-cell-volume-disorders
#19
REVIEW
Catherine Badens, Hélène Guizouarn
Genetic defects of erythrocyte transport proteins cause disorders of red blood cell volume that are characterized by abnormal permeability to the cations Na(+) and K(+) and, consequently, by changes in red cell hydration. Clinically, these disorders are associated with chronic haemolytic anaemia of variable severity and significant co-morbidities, such as iron overload. This review provides an overview of recent insights into the molecular basis of this group of rare anaemias involving cation channels and transporters dysfunction...
September 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27321926/tentonin-3-tmem150c-confers-distinct-mechanosensitive-currents-in-dorsal-root-ganglion-neurons-with-proprioceptive-function
#20
Gyu-Sang Hong, Byeongjun Lee, Jungwon Wee, Hyeyeon Chun, Hyungsup Kim, Jooyoung Jung, Joo Young Cha, Tae-Ryong Riew, Gyu Hyun Kim, In-Beom Kim, Uhtaek Oh
Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics...
July 6, 2016: Neuron
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