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      Role of Transient Receptor Potential Vanilloid 4 Channel in Skin Physiology and Pathology

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          Abstract

          Transient receptor potential vanilloid 4 (TRPV4) channel responds to temperature, as well as various mechanical and chemical stimuli. This non-selective cation channel is expressed in several organs, including the blood vessels, kidneys, oesophagus and skin. In the skin, TRPV4 channel is present in various cell types such as keratinocytes, melanocytes and sensory neurons, as well as immune and inflammatory cells, and engages in several physiological actions, from skin homeostasis to sensation. In addition, there is substantial evidence implicating dysfunctional TRPV4 channel—in the form of either deficient or excessive channel activity—in pathological cutaneous conditions such as skin barrier compromise, pruritus, pain, skin inflammation and carcinogenesis. These varied functions, combined with the fact that TRPV4 channel owns pharmacologically-accessible sites, make this channel an attractive therapeutic target for skin disorders. In this review, we summarize the different physiological and pathophysiological effects of TRPV4 in the skin.

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          Most cited references84

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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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            Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.

            The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nervous system, the channel is expressed in neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells.
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              The vanilloid receptor: a molecular gateway to the pain pathway.

              The detection of painful stimuli occurs primarily at the peripheral terminals of specialized sensory neurons called nociceptors. These small-diameter neurons transduce signals of a chemical, mechanical, or thermal nature into action potentials and transmit this information to the central nervous system, ultimately eliciting a perception of pain or discomfort. Little is known about the proteins that detect noxious stimuli, especially those of a physical nature. Here we review recent advances in the molecular characterization of the capsaicin (vanilloid) receptor, an excitatory ion channel expressed by nociceptors, which contributes to the detection and integration of pain-producing chemical and thermal stimuli. The analysis of vanilloid receptor gene knockout mice confirms the involvement of this channel in pain sensation, as well as in hypersensitivity to noxious stimuli following tissue injury. At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain.
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                Author and article information

                Journal
                Sultan Qaboos Univ Med J
                Sultan Qaboos Univ Med J
                Sultan Qaboos University Medical Journal
                Sultan Qaboos University Medical Journal, College of Medicine & Health Sciences
                2075-051X
                2075-0528
                May 2020
                28 June 2020
                : 20
                : 2
                : e138-e146
                Affiliations
                Department of Physiology, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
                Author notes
                [* ]Corresponding Author’s e-mail: boudaka@ 123456squ.edu.om
                Article
                squmj2005-e138-146
                10.18295/squmj.2020.20.02.003
                7328835
                32655905
                ba2ec0fd-73d8-4bac-b206-1c52820a686b
                © Copyright 2020, Sultan Qaboos University Medical Journal, All Rights Reserved

                This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.

                History
                : 28 July 2019
                : 17 September 2019
                : 03 November 2019
                : 03 December 2019
                Categories
                Review

                trpv4,skin,epidermis,keratinocytes,pain,pruritis,melanoma
                trpv4, skin, epidermis, keratinocytes, pain, pruritis, melanoma

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