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      TRPV Subfamily (TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) Gene and Protein Expression in Patients with Ulcerative Colitis

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          Abstract

          Introduction

          TRPVs are a group of receptors with a channel activity predominantly permeable to Ca 2+. This subfamily is involved in the development of gastrointestinal diseases such as ulcerative colitis (UC). The aim of the study was to characterize the gene and protein expression of the TRPV subfamily in UC patients and controls.

          Methods

          We determined by quantitative PCR the gene expression of TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 in 45 UC patients (29 active UC and 16 remission UC) and 26 noninflamed controls. Protein expression was evaluated in 5  μm thick sections of formalin-fixed, paraffin-embedded tissue from 5 customized severe active UC patients and 5 control surgical specimens.

          Results

          TRPV2 gene expression was increased in the control group compared with active UC and remission patients ( P = 0.002 and P = 0.05, respectively). TRPV3 gene expression was significantly higher in controls than in active UC patients ( P = 0.002). The gene expression of TRPV4 was significantly higher in colonic tissue from patients with remission UC compared with active UC patients ( P = 0.05) and controls ( P = 0.005). TRPV5 had significantly higher mRNA levels in a control group compared with active UC patients ( P = 0.02). The gene expression of TRPV6 was significantly higher in the colonic tissue from patients with active UC compared with the control group ( P = 0.05). The protein expression of TRPV2 was upregulated in the mucosa and submucosa from the controls compared with the UC patients ( P ≤ 0.003). The protein expression of TRPV3 and TRPV4 was upregulated in all intestinal layers from the controls compared with the UC patients ( P < 0.001). TRPV5 was upregulated in the submucosa and serosa from the controls vs. UC patients ( P < 0.001). TRPV6 was upregulated in all intestinal layers from the UC patients vs. controls ( P ≤ 0.001).

          Conclusion

          The TRPV subfamily clearly showed a differential expression in the UC patients compared with the controls, suggesting their role in the pathophysiology of UC.

          Related collections

          Most cited references25

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          TRP channels.

          The TRP (Transient Receptor Potential) superfamily of cation channels is remarkable in that it displays greater diversity in activation mechanisms and selectivities than any other group of ion channels. The domain organizations of some TRP proteins are also unusual, as they consist of linked channel and enzyme domains. A unifying theme in this group is that TRP proteins play critical roles in sensory physiology, which include contributions to vision, taste, olfaction, hearing, touch, and thermo- and osmosensation. In addition, TRP channels enable individual cells to sense changes in their local environment. Many TRP channels are activated by a variety of different stimuli and function as signal integrators. The TRP superfamily is divided into seven subfamilies: the five group 1 TRPs (TRPC, TRPV, TRPM, TRPN, and TRPA) and two group 2 subfamilies (TRPP and TRPML). TRP channels are important for human health as mutations in at least four TRP channels underlie disease.
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            A capsaicin-receptor homologue with a high threshold for noxious heat.

            Pain-producing heat is detected by several classes of nociceptive sensory neuron that differ in their thermal response thresholds. The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 degrees C) thermal stimuli. VR1 is also activated by protons, indicating that it may participate in the detection of noxious thermal and chemical stimuli in vivo. Here we identify a structurally related receptor, VRL-1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is activated by high temperatures, with a threshold of approximately 52 degrees C. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium- to large-diameter neurons, making it a candidate receptor for transducing high-threshold heat responses in this class of cells. VRL-1 transcripts are not restricted to the sensory nervous system, indicating that this channel may be activated by stimuli other than heat. We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.
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              TRPV4 calcium entry channel: a paradigm for gating diversity.

              The vanilloid receptor-1 (VR1, now TRPV1) was the founding member of a subgroup of cation channels within the TRP family. The TRPV subgroup contains six mammalian members, which all function as Ca2+ entry channels gated by a variety of physical and chemical stimuli. TRPV4, which displays 45% sequence identity with TRPV1, is characterized by a surprising gating promiscuity: it is activated by hypotonic cell swelling, heat, synthetic 4alpha-phorbols, and several endogenous substances including arachidonic acid (AA), the endocannabinoids anandamide and 2-AG, and cytochrome P-450 metabolites of AA, such as epoxyeicosatrienoic acids. This review summarizes data on TRPV4 as a paradigm of gating diversity in this subfamily of Ca2+ entry channels.
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                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2020
                8 May 2020
                : 2020
                : 2906845
                Affiliations
                1Inflammatory Bowel Disease Clinic. Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                2MD/PhD Program (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Ciudad Universitaria 3000, C.P. 04360 Coyoacán, México City, Mexico
                3Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                4Department of Endoscopy, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                5Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                6Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                Author notes

                Academic Editor: Francesca Santilli

                Author information
                https://orcid.org/0000-0002-7489-2596
                https://orcid.org/0000-0001-5804-7221
                https://orcid.org/0000-0002-8925-8651
                https://orcid.org/0000-0001-8553-1027
                https://orcid.org/0000-0002-5247-5812
                Article
                10.1155/2020/2906845
                7231094
                b1427326-4435-43ae-90af-1144fe513b81
                Copyright © 2020 Joel J. Toledo Mauriño et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 October 2019
                : 4 March 2020
                : 11 April 2020
                Funding
                Funded by: Universidad Nacional Autónoma de México
                Funded by: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
                Categories
                Research Article

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