Transient Receptor Potential Vanilloid 4 (TRPV4) Is Downregulated in Keratinocytes in Human Non-Melanoma Skin Cancer

Fusi, Camilla; Materazzi, Serena; Minocci, D.; Maio, Vincenza; Oranges, Teresa; Massi, Daniela; Nassini, Romina

doi:10.1038/jid.2014.145

Cited by 70 publications

(70 citation statements)

References 68 publications

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“…The thermosensitive TRPV4 channel is a swell-activated osmolarity sensor [97,98,119]. TRPV4 immunoreactivity was shown in human nerve fibers [120,115] and human skin [120,121]. Our RNA-Seq analysis revealed weak TRPV4 expression in all four human TG samples and the DRG with FPKM values comparable to that of TRPV3 (Fig 6A).…”

Section: Resultsmentioning

confidence: 84%

RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

Flegel

Schöbel

Altmüller³

et al. 2015

PLoS ONE

158

168

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The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq) to conduct the first expression analysis of human trigeminal ganglia (TG) and dorsal root ganglia (DRG). We analyzed the data with a focus on G-protein coupled receptors (GPCRs) and ion channels, which are (potentially) involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP) channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs) with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues.

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Section: Resultsmentioning

confidence: 84%

RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

Flegel

Schöbel

Altmüller³

et al. 2015

PLoS ONE

158

168

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“…Surely, they are no atavism because several functions of these receptors could be identified, for example regulation of barrier homoeostasis. Nevertheless, the broad function spectrum of these ectopic receptors is only marginally analysed to date . According to these results, also more ectopically expressed human ORs have been identified, and the functionality of ORs in non‐olfactory cell types has become better understood .…”

Section: Discussionmentioning

confidence: 99%

“…Remarkably, also a wide range of classic central nervous system (CNS) neuroreceptors, which are usually necessary for auditory and visual functions, could be found in the skin, such as opsin receptors and transient receptor potential channels. They seem to play an important role, for example, in permeability barrier homoeostasis, but their full function is also still under investigation …”

Section: Introductionmentioning

confidence: 99%

Two olfactory receptors—OR2A4/7 andOR51B5—differentially affect epidermal proliferation and differentiation

Tsai

Veitinger

Peek

et al. 2016

Experimental Dermatology

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Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.

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“…TRPV4 mRNA and immunohistochemical staining are reduced in premalignant skin lesions and in basal and squamous cell carcinomas [130]. Whether there is a functional role for TRPV4 in tumorigenesis has yet to be determined.…”

Section: Contributions Of Trp Channels To Skin Biology and Pathophmentioning

confidence: 99%

TRP Channels in Skin Biology and Pathophysiology

Caterina¹,

Pang²

2016

Pharmaceuticals

137

126

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Ion channels of the Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or divalent cations into cells in response to a host of chemical or physical stimuli. In the skin, TRP channels are expressed in many cell types, including keratinocytes, sensory neurons, melanocytes, and immune/inflammatory cells. Within these diverse cell types, TRP channels participate in physiological processes ranging from sensation to skin homeostasis. In addition, there is a growing body of evidence implicating abnormal TRP channel function, as a product of excessive or deficient channel activity, in pathological skin conditions such as chronic pain and itch, dermatitis, vitiligo, alopecia, wound healing, skin carcinogenesis, and skin barrier compromise. These diverse functions, coupled with the fact that many TRP channels possess pharmacologically accessible sites, make this family of proteins appealing therapeutic targets for skin disorders.

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Transient Receptor Potential Vanilloid 4 (TRPV4) Is Downregulated in Keratinocytes in Human Non-Melanoma Skin Cancer

Cited by 70 publications

References 68 publications

RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

Two olfactory receptors—OR2A4/7 andOR51B5—differentially affect epidermal proliferation and differentiation

TRP Channels in Skin Biology and Pathophysiology

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