Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

doi:10.5056/jnm16114

Cited by 34 publications

(36 citation statements)

References 26 publications

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“…In light of their physiological importance, both gain-of-function and loss-of-function mutations of Piezo channels have been associated with pathological conditions such as xerocytosis 11 , 14 – 16 , arthrogryposis 17 – 23 , and lymphedema 24 . Recent studies suggest Piezo channels may also have important roles in other conditions such as sleep apnea 25 and hyperalgesia 26 – 29 .…”

Section: Introductionmentioning

confidence: 99%

Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1

2018

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Piezo proteins are transmembrane ion channels which transduce many forms of mechanical stimuli into electrochemical signals. Their pore, formed by the assembly of three identical subunits, opens by an unknown mechanism. Here, to probe this mechanism, we investigate the interaction of Piezo1 with the small molecule agonist Yoda1. By engineering chimeras between mouse Piezo1 and its Yoda1-insensitive paralog Piezo2, we first identify a minimal protein region required for Yoda1 sensitivity. We next study the effect of Yoda1 on heterotrimeric Piezo1 channels harboring wild type subunits and Yoda1-insensitive mutant subunits. Using calcium imaging and patch-clamp electrophysiology, we show that hybrid channels harboring as few as one Yoda1-sensitive subunit exhibit Yoda1 sensitivity undistinguishable from homotrimeric wild type channels. Our results show that the Piezo1 pore remains fully open if only one subunit remains activated. This study sheds light on the gating and pharmacological mechanisms of a member of the Piezo channel family.

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Section: Introductionmentioning

confidence: 99%

Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1

2018

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“…PIEZO1 and PIEZO2 are two mechano-sensitive cation channels that play a key role in cell number regulation 153 , 154 and migration 155 , hearing 156 , neural 157 and vascular 158 development, somatosensory functions 159 , proprioception 160 and beyond. Piezo channels have been recently associated with multiple pathologies like arthrogryposis 161 , apnea 162 , congenital lymphatic dysplasia 163 , hyperalgesia 164 , 165 , malaria 166 , pancreatitis 167 , xerocytosis 168 , Gordon syndrome, Marden-Walker Syndrome, and Distal Arthrogryposis Type 5 169 . The discovery of mechanotransduction signalling pathways has received notable attention in the last years and may open the door to new therapeutic strategies to treat these diseases 147 .…”

Section: Discussionmentioning

confidence: 99%

TrendyGenes, a computational pipeline for the detection of literature trends in academia and drug discovery

Nájera

Carlón

Crowther

2021

Sci Rep

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Target identification and prioritisation are prominent first steps in modern drug discovery. Traditionally, individual scientists have used their expertise to manually interpret scientific literature and prioritise opportunities. However, increasing publication rates and the wider routine coverage of human genes by omic-scale research make it difficult to maintain meaningful overviews from which to identify promising new trends. Here we propose an automated yet flexible pipeline that identifies trends in the scientific corpus which align with the specific interests of a researcher and facilitate an initial prioritisation of opportunities. Using a procedure based on co-citation networks and machine learning, genes and diseases are first parsed from PubMed articles using a novel named entity recognition system together with publication date and supporting information. Then recurrent neural networks are trained to predict the publication dynamics of all human genes. For a user-defined therapeutic focus, genes generating more publications or citations are identified as high-interest targets. We also used topic detection routines to help understand why a gene is trendy and implement a system to propose the most prominent review articles for a potential target. This TrendyGenes pipeline detects emerging targets and pathways and provides a new way to explore the literature for individual researchers, pharmaceutical companies and funding agencies.

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“…The PIEZO1 receptor is involved in endothelial function and development ( Li et al, 2014 ; Rode et al, 2017 ) as well as cardiovascular homeostasis ( Rode et al, 2017 ). PIEZO2 receptors have a role in the function of the somatosensory apparatus involved in proprioception ( Yang et al, 2016 ), pain sensation ( Bai et al, 2017 ), and possibly as a coreceptor with PIEZO1 in the carotid sinus ( Zeng et al, 2018 ).…”

Section: Mechanotransduction By the Carotid Sinusmentioning

confidence: 99%

The Rheology of the Carotid Sinus: A Path Toward Bioinspired Intervention

Iskander

Bilgi

Naftalovich

et al. 2021

Front. Bioeng. Biotechnol.

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The association between blood viscosity and pathological conditions involving a number of organ systems is well known. However, how the body measures and maintains appropriate blood viscosity is not well-described. The literature endorsing the function of the carotid sinus as a site of baroreception can be traced back to some of the earliest descriptions of digital pressure on the neck producing a drop in blood delivery to the brain. For the last 30 years, improved computational fluid dynamic (CFD) simulations of blood flow within the carotid sinus have demonstrated a more nuanced understanding of the changes in the region as it relates to changes in conventional metrics of cardiovascular function, including blood pressure. We suggest that the unique flow patterns within the carotid sinus may make it an ideal site to transduce flow data that can, in turn, enable real-time measurement of blood viscosity. The recent characterization of the PIEZO receptor family in the sinus vessel wall may provide a biological basis for this characterization. When coupled with other biomarkers of cardiovascular performance and descriptions of the blood rheology unique to the sinus region, this represents a novel venue for bioinspired design that may enable end-users to manipulate and optimize blood flow.

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Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

Cited by 34 publications

References 26 publications

Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1

Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1

TrendyGenes, a computational pipeline for the detection of literature trends in academia and drug discovery

The Rheology of the Carotid Sinus: A Path Toward Bioinspired Intervention

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