TRP ion channels in the pathobiology of disease

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  Increased transient receptor potential canonical 3 activity is involved in the pathogenesis of detrusor overactivity by dynamic interaction with Na⁺/Ca²⁺ exchanger 1

  The expression and functional levels of TRPC3, a nonselective cation channel, and NCX1, a Na⁺/Ca2⁺ exchanger, are increased in the bladders of rats with partial bladder outlet obstruction-induced detrusor overactivity. The synergistic effects of TRPC3 and NCX1 significantly increase the concentration of Ca²⁺_i in smooth muscle cells, which induces bladder hyperactivity in this animal model of overactive bladder. TRPC3 and NCX1 may be new therapeutic targets for detrusor overactivity.

  • Jingzhen Zhu
  • Yi Fan
  • Jie Xu

  Article8 Sep 2021 Laboratory Investigation
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  Amelioration of circadian disruption and calcium-handling protein defects by choline alleviates cardiac remodeling in abdominal aorta coarctation rats

  Choline attenuates abdominal aortic coarctation-induced cardiac remodeling and cardiac dysfunction, by amelioration of circadian rhythm disruption and attenuation of calcium-handling protein defects. Modulation of vagal activity by choline may have therapeutic potential for cardiac remodeling and heart failure.

  • Xi He
  • Si Yang
  • Wei-Jin Zang

  Article1 Mar 2021 Laboratory Investigation
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  Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice

  Serotonin (5-HT) is an important mediator of tissue edema and inflammation. The authors used mouse models and cell-based signaling assays to provide greater understanding of the mechanisms involved. They demonstrate that effects of 5-HT are mediated through the 5-HT_2A receptor and involve activation of the mechanosensitive ion channel TRPV4 and neuropeptide release.

  • Jeffri S. Retamal
  • Megan S. Grace
  • Peter McIntyre

  Article15 Apr 2021 Laboratory Investigation
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  L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes

  Human corneal keratocytes (HCK) are essential for maintaining corneal structure and transparency. This study shows that the natural antioxidant L-carnitine inhibits stromal scarring by suppressing injury-induced intrinsic transient receptor potential vanilloid type 1 (TRPV1) activity that is linked to induction of myofibroblast transdifferentiation in HCK cells. Blocking TRPV1 activation on keratocytes may therefore be a viable approach to suppress corneal opacification in a clinical setting.

  • Elizabeth Turan
  • Monika Valtink
  • Stefan Mergler

  ArticleOpen Access26 Feb 2021 Laboratory Investigation
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  Ascorbate-induced oxidative stress mediates TRP channel activation and cytotoxicity in human etoposide-sensitive and -resistant retinoblastoma cells

  Ascorbate can act as an oxidant to induce tumor cell death at a pharmacological dose. Here the authors show that this response is associated with increases in GPCR Gi/o activity. This effect promotes rises in intracellular Ca²⁺ influx through transient receptor potential channel activity in retinoblastoma cells.

  • Jakub Oronowicz
  • Jacqueline Reinhard
  • Stefan Mergler

  ArticleOpen Access18 Sep 2020 Laboratory Investigation
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  The transient receptor potential vanilloid 4 (TRPV4) ion channel mediates protease activated receptor 1 (PAR1)-induced vascular hyperpermeability

  The thrombin receptor PAR1 and mechanosensitve ion channel TRPV4 are known to modulate endothelial barriers and contribute to edema, but functional interactions between these targets are not well understood. Utilizing cell signalling studies and in vivo models, the authors have demonstrated that PAR1 activation leads to functional upregulation of endothelial TRPV4 activity, to promote vascular leakage in airways and the gastrointestinal system.

  • Scott Peng
  • Megan S. Grace
  • Peter McIntyre

  Article27 Apr 2020 Laboratory Investigation
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  Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4

  The trigeminal sensory nerve is critical for maintenance of corneal epithelial stem cells in the corneal limbus and is essential to the homeostasis of the tissue. TRPV4 signal mediated gene expression in the nerve drives expression of stem cell markers and nerve growth factor in the limbal stem cells as well as potentiates their proliferation.

  • Yuka Okada
  • Takayoshi Sumioka
  • Shizuya Saika

  Article9 Nov 2018 Laboratory Investigation
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  Differential engagement of ORAI1 and TRPC1 in the induction of vimentin expression by different stimuli

  The calcium signal is a regulator of the acquisition of a more mesenchymal phenotype. Our work in MDA-MB-468 breast cancer cells identifies a complex relationship between factor-specific induction of the epithelial–mesenchymal marker vimentin and the differential involvement of the canonical store-operated calcium channel ORAI1 and the calcium channel component TRPC1.

  • Teneale A. Stewart
  • Iman Azimi
  • Gregory R. Monteith

  Article26 Jun 2019 Laboratory Investigation
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  TRPM7 mediates kidney injury, endothelial hyperpermeability and mortality during endotoxemia

  Acute kidney injury and endothelial hyperpermeability are main features observed during severe sepsis with low survival rate. Transient receptor potential melastatin 7 (TRPM7) calcium channel inhibition protects against endotoxemia-induced kidney injury potentially by means of endothelial hyperpermeability decreasing. Remarkably, TRPM7 inhibition improves survival in endotoxemic animals.

  • Sebastian Gatica
  • Vicente Villegas
  • Felipe Simon

  Article23 Aug 2019 Laboratory Investigation
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  Selective Ah receptor modulators attenuate NPC1L1-mediated cholesterol uptake through repression of SREBP-2 transcriptional activity

  The Niemann–Pick C1-like intracellular cholesterol transporter gene and a number of genes in the cholesterol synthesis pathway are transcriptionally regulated by SREBP-2. The liganded Ah receptor increases proteolytic turnover of transcriptionally active SREBP2. Thus, Ah receptor ligands are capable of attenuating cholesterol uptake into Caco-2 cells.

  • Gulsum E. Muku
  • Ann Kusnadi
  • Gary H. Perdew

  Article15 Aug 2019 Laboratory Investigation
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  TRPV4 is dispensable for the development of airway allergic asthma

  Allergic asthma is one of the most common immune-mediated disorders. The authors investigated the possibility that TPRV4 cation channels facilitate the development of allergic asthma and subsequent pulmonary fibrosis in the lung. Their data suggest that TPRV4 is dispensable in the initiation and development of airway asthma and subsequent fibrosis.

  • Senthilkumar Palaniyandi
  • Arunraj M. Rajendrakumar
  • Shaik O. Rahaman

  Article15 Aug 2019 Laboratory Investigation

• Role of macrophage TRPV4 in inflammation

  Transient receptor ion channels have emerged as critical channels/receptors in numerous physiological and pathological conditions. In this paper the authors discuss our current understanding of the role of macrophage transient receptor potential channel subfamily V member 4 (TRPV4) in various inflammatory conditions.

  • Bidisha Dutta
  • Rakesh K. Arya
  • Shaik O. Rahaman

  Review Article23 Oct 2019 Laboratory Investigation
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  The TRPV2 cation channels: from urothelial cancer invasiveness to glioblastoma multiforme interactome signature

  • Giorgio Santoni
  • Consuelo Amantini
  • Maria Beatrice Morelli

  Review Article25 Oct 2019 Laboratory Investigation
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  Temperature elevation in epileptogenic foci exacerbates epileptic discharge through TRPV4 activation

  The authors reveal that TRPV4, a thermosensitive ion channel, is constitutively active in the brain. They found that local brain temperature is increased at epileptogenic foci, and that hyperthermia lead TRPV4 over-activation and hyper-neuronal activities. Notably, brain cooling treatment drastically suppresses epileptic discharges dependent on the inactivation of TRPV4.

  • Koji Shibasaki
  • Katsuya Yamada
  • Yasuki Ishizaki

  Article22 Oct 2019 Laboratory Investigation
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  Vascular endothelial growth factor enhances profibrotic activities through modulation of calcium homeostasis in human atrial fibroblasts

  Vascular endothelial growth factor increases the profibrotic activity of atrial fibroblasts by activating the currents through transient receptor potential channels and intermediate-conductance calcium-activated K⁺ (K_Ca3.1) channels and by enhancing Ca²⁺ entry-induced phosphorylated Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) signaling. These findings suggest a novel strategy targeting atrial myopathy and arrhythmofibrosis.

  • Cheng-Chih Chung
  • Yung-Kuo Lin
  • Yi-Jen Chen

  Article20 Nov 2019 Laboratory Investigation
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  TRPC5 regulates axonal outgrowth in developing retinal ganglion cells

  This study shows that TRPC5 is an important negative regulator of retinal ganglion cell (RGC) axonal outgrowth and an important regulator of neurite remodeling. The authors hypothesize that TRPC5 senses abnormal intraocular pressure changes and contributes to the death of RGCs in disease. In glaucoma, for example, excessive Ca2+ entry through TRPC5 might induce dendritic and axonal remodeling, which could lead to cell death.

  • Mai Oda
  • Hanako Yamamoto
  • Koji Shibasaki

  Article16 Dec 2019 Laboratory Investigation
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  Transient receptor potential cation channel subfamily V and breast cancer

  Transient receptor potential cation channel subfamily V (TRPV) can be overexpressed in breast cancer. TRPV channels play important roles in breast cancer cell proliferation, migration, and cell death as well as the tumor microenvironment and cancer-associated pain. This review provides an overview of TRPV channels in the context of breast cancer.

  • Choon Leng So
  • Michael J. G. Milevskiy
  • Gregory R. Monteith

  Review Article10 Dec 2019 Laboratory Investigation
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  TRPV2 channel as a possible drug target for the treatment of heart failure

  Transient receptor potential vanilloid 2 (TRPV2) plays a significant role in the onset and progression of heart failure. In this review, the authors summarize the recent findings on TRPV2 in cardiomyocytes and immune cells involved in the development of heart failure and discuss the current progress of drug development that is aimed at treating heart failure through targeting TRPV2.

  • Yuko Iwata
  • Shin Ito
  • Masafumi Kitakaze

  Review Article19 Dec 2019 Laboratory Investigation
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  The TRPV4-AKT axis promotes oral squamous cell carcinoma cell proliferation via CaMKII activation

  This paper shows that TRPV4, a Ca²⁺-permeable nonselective cation channel, responds to extracellular environments to regulate oral squamous cell carcinoma cellular growth through CaMKII/AKT activity in vitro and in vivo.

  • Shinsuke Fujii
  • Yudai Tajiri
  • Tamotsu Kiyoshima

  Article19 Dec 2019 Laboratory Investigation
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  TRPV4 activation by thermal and mechanical stimuli in disease progression

  The authors review the data which describe how the deletion of TRPV4 evokes abnormal behavior in mice. These studies demonstrate that the maintenance of body temperature and the sensory system for detecting body temperature, such as via TRPV4, are critical components for normal cellular function.

  • Koji Shibasaki

  Review Article2 Jan 2020 Laboratory Investigation
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  Production of TRPV2-targeting functional antibody ameliorating dilated cardiomyopathy and muscular dystrophy in animal models

  The authors generated a functional monoclonal antibody that recognizes and promotes the internalization of TRPV2 to reduce TRPV2-driven Ca²⁺ influx. Using cardiomyopathic/muscular dystrophic animal models, they confirmed the beneficial effects of this antibody, which includes improvements in both Ca²⁺ handling in cardiomyocytes and in skeletal muscle properties.

  • Yuko Iwata
  • Shigeo Wakabayashi
  • Masafumi Kitakaze

  Article2 Jan 2020 Laboratory Investigation