Identification and expression of transient receptor potential (TRP) genes in Urechis unicinctus and the role of TRPC5 in immune response.

The transient receptor potential (TRP) field began with the analysis of a spontaneously formed Drosophila mutant showing transient, rather than sustained, responses to prolonged intense illumination in electroretinogram (ERG) measurements, rendering the flies effectively blind. The physiological activation of the Drosophila TRP and TRPL channels by light is characterized by an outstanding performance. To function as a reliable light monitor, each stage of the phototransduction cascade needs an efficient mechanism of activation as well as an equally efficient mechanism of termination, ensuring that, at the cessation of the light stimulus, the photoreceptor potential will rapidly reach dark baseline. The essential role of Drosophila trp in vision was discovered by the isolation of a spontaneous mutation and large-scale genetic screening. Channel members of the TRP superfamily are involved in fundamental mechanisms common to many cells and tissues, especially where cellular Ca2+ plays an important role.

513 Background: Different factors are effective in the development of colorectal cancer (CC). With the discovery of that TRP (transient receptor potential) genes family is an important component of calcium channel, about 30 members of the family of TRP ion channel in mammals have been determined up to the present. TRP channels are associated with many pathological conditions like cancer and cardiovascular diseases as well as the physiological significance of them.. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CC patients and to analyze the relationship of expression in tumor tissue of colorectal cancer with other known prognostic factors. Methods: In this study, 93 CC patients whose follow-up and treatment realized in Medical Oncology Department of Gaziantep University Medical Faculty Hospital were analyzed retrospectively. Level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples of 93 patients were studied at the level of mRNA with real-time PCR. Results: From normal and cancerous colorectal tissues of 37 female and 56 male patients diagnosed with colorectal cancer, expressions of TRPV3, TRPV4, TRPV5, TRPM4, and TRPC6 genes in tumor tissue were detected lower when compared to normal tissue (p < 0.05). When expression levels of other TRP genes in tissues were compared, any significant difference was not found (p > 0.05). There was no meaningful difference between prognostic factors and gene expressions of tumor tissues statistically (p > 0.05). Conclusions: Expression of many proteins in cancer cells compared to normal cells increases or decreases. In CC, TRPV3, TRPV4, TRPV5, TRPM4, and TRPC6 genes of which expression in cancerous tissue decreases may be thought as potential genes contributing to tumorigenesis. To verify this hypothesis, it should be supported with further studies.

Transient receptor potential (TRP) channels play critical roles in animals in sensing diverse stimuli, especially environmental temperature. The teleost fish Nile tilapia (Oreochromis niloticus) cannot tolerate cold temperatures. In this study, we identified a total of 32 TRP genes in the tilapia genome. Based on analyses of gene structure and phylogenetic relationship, all tilapia TRP genes could be classified into six subfamilies, namely, TRPA, TRPC, TRPM, TRPV, TRPP, and TRPML. Comparative analysis showed that three TRP subfamilies-TRPC, TRPM, and TRPML-underwent an expansion in tilapia and other teleost fishes following three or four rounds of whole-genome duplication. In addition, expression profiling revealed that a large number of TRP genes were expressed in at least one tissue in adult tilapia. Notably, compared with normal growth temperature (28 °C), cold stress (10 °C) altered the expression of several TRPs in multiple tissues in adult tilapia, especially upregulating TRPC5 in the brain and TRPM7 in the gill. Collectively, these findings provide new insight into the phylogeny of TRP genes in animals and lay the foundation for further investigation into the roles of TRP channels in cold sensitivity in tilapia.

Genome-wide characterization of the TRP gene family and transcriptional expression profiles under different temperatures in gecko Hemiphyllodactylus yunnanensis.

Transient receptor potential (TRP) genes have been implicated in a wide array of human disorders, from cancers to bipolar disorder. The extraordinary range of diseases in whose pathogenesis they may play a role exemplifies the equally broad range of functions of the TRP proteins. TRP proteins primarily form homomeric or heteromeric channels in the cell membrane but there may also be intracellular non-channel functions for TRPs. Mutations in TRP genes have been causally associated with at least 12 hereditary human diseases. This chapter aims to summarise those associations and focuses on the following diseases: focal segmental glomerulosclerosis; polycystic kidney disease; brachyolmia; spondylometaphyseal dysplasia; metatropic dysplasia; hereditary motor and sensory neuropathy; spinal muscular atrophy; congenital stationary night blindness; progressive familial heart block; hypomagnesaemia; and mucolipidosis. There appears to be very little to connect these disorders except the involvement of a TRP gene but by understanding more about the genes involved in diseases, we understand more about disease biology and about the function of those genes causally associated. This feedback loop of information will serve to enhance our knowledge of disease and elucidate basic gene and protein function of the TRPs.

Transient-receptor potential (TRP) channels comprise a diverse family of ion channels, which play important roles in regulation of intracellular calcium. Emerging evidence has revealed the critical roles of TRP channels in tumor development and progression. However, we still lack knowledge about the genetic and pharmacogenomics landscape of TRP genes across cancer types. Here, we comprehensively characterized the genetic and transcriptome alterations of TRP genes across >10,000 patients of 33 cancer types. We revealed prevalent somatic mutations and copy number variation in TRP genes. In particular, mutations located in transmembrane regions of TRP genes were likely to be deleterious mutations (p-values < 0.001). Genetic alterations were correlated with transcriptome dysregulation of TRP genes, and we found that TRPM2, TRPM8, and TPRA1 showed extent dysregulation in cancer. Patients with TRP gene alterations were with significantly higher hypoxia scores, tumor mutation burdens, tumor stages and grades, and poor survival. The alterations of TRP genes were significantly associated with the activity of cancer-related pathways. Moreover, we found that the expression of TRP genes were potentially useful for development of targeted therapies. Our study provided the landscape of genomic and transcriptomic alterations of TPRs across 33 cancer types, which is a comprehensive resource for guiding both mechanistic and therapeutic analyses of the roles of TRP genes in cancer. Identifying the TRP genes with extensive genetic alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.

The transient receptor potential (TRP) gene family is vital to cellular physiology, mediating ion flow across membranes and facilitating sensory signal transduction. This article examines the transcriptomic landscape of TRP genes, emphasizing their varying expression across organs, tissues, and cells, with a particular focus on the brain. Analysis reveals a distinct spatial distribution of TRP gene expression, notably enriched in the hippocampus during brain development, highlighting their essential role in neuronal function. Utilizing datasets from the Human Protein Atlas, Allen Human Brain Atlas, and studies on aging and dementia, associations are identified between TRP gene expression and the development or pathophysiology of neural tissue, highlighting the therapeutic potential of TRP channels in addressing, e.g., sensory impairments and cognitive decline. These insights into the regulatory dynamics of TRP channels lay a foundation for developing targeted interventions for neurodegenerative disorders.

Acute pancreatitis (AP) is a severe inflammatory disease. Transient receptor potential (TRP) channels have been reported to participate in various pathophysiological processes. However, the role of TRP channels in the AP remains unclear. Here, we investigated the involvement of TRP channels in AP. We identified differentially expressed genes (DEGs) using the public AP datasets GSE3644 and GSE109227 and identified 20 hub genes. We analyzed their correlation with the TRP genes. Four DEGs related to TRP channels were selected, and functional enrichment analyses were conducted. An interaction network involving the transcription factors, microRNAs (miRNAs), and mRNA of the four TRP-associated genes was established. To evaluate the diagnostic effectiveness, receiver operating characteristic (ROC) analysis and machine learning (ML) methods, such as support vector classifiers and random forest, were applied. Furthermore, we analyzed immune cell infiltration and its relationship with the four TRP genes. To confirm these bioinformatics findings, we performed invitro and invivo experiments using primary acinar cells and an experimental mouse model of AP. Four TRP-related genes, namely, MCOLN1, MCOLN3, TRPM7, and TRPV4, were selected for the correlation analysis. Functional analyses showed that these four genes are involved in cellular senescence and the calcium signaling pathway. A TF-miRNA-mRNA interaction network was constructed for the four TRP-associated genes. The areas under the ROC curves (AUC) of MCOLN1, MCOLN3, TRPM7, and TRPV4 were 0.833, 0.700, 1.0, and 1.0, respectively. ML algorithms performed well in predicting AP with AUCs ≥ 0.67. TRPM7, TRPV4, and MCOLN3 are associated with immune cell infiltration of AP tissues. Using experimental AP models, we found that the expression of three TRP-related genes, MCOLN1, TRPM7, and TRPV4, was significantly upregulated in mouse AP tissues. Specifically, TRPM7 knockdown or inhibition by its inhibitor 2-APB significantly reduced pancreatic acinar cell damage, inflammatory mediator expression, and mRNA levels of senescence-associated genes. Our study suggests that TRP-related genes play crucial roles in AP and may be promising biomarkers for predicting the pathogenesis of AP.

Membrane ion channels are critical mediators of vascular endothelial and smooth muscle cell function and regulate diverse properties of blood vessels such as arterial tone, angiogenesis, and permeabilty. Although physiological roles for many ion channels and transporters are well established, the functional significance of transient receptor potential (TRP) channels in the vasculature is just beginning to be elucidated. This chapter summarizes the current understanding of these cation channels in vascular function. For a more in-depth overview of TRP channel biology, the reader is directed to several excellent general reviews covering this topic [1–4].As shown in Table 26.1, the mammalian TRP superfamily of cation channels contains at least 22 genes grouped into three major subfamilies based on sequence homology: TRPV (vanilloid), TRPC (canonical), and TRPM (melastatin). Three additional subfamilies (the “distant TRPs”), TRPP (polycystin), TRPML (mucolipin), and TRPA have been proposed, bringing the total number of TRP-related proteins to around 30. Although these channels were initially described in sensory neurons, it is now thought that most cell types express several TRP genes. TRP proteins are expressed as six transmembrane-domain polypeptide subunits, and it is believed that four subunits assemble in the plasma membrane to form functional channels. All TRP channels are cation permeable, and most are not selective for monovalent versus divalent ions. Exceptions include TRPV5 and TRPV6, which display significant specificity for Ca2+ ions, and TRPM4 and TRPM5, which are highly selective for monovalent cations and impermeant to Ca2+ TRP channels are activated by a variety of stimuli, including changes in pressure, temperature, osmolarity, and intracellular Ca2+ Fatty acids and receptor-dependent vasoconstrictor agonists also activate vascular TRP channels. This diversity of ionic conductivity and activating mechanisms is consistent with the possibility that members of the TRP superfamily may contribute to regulation of a variety of physiological systems.Elucidation of functional roles for TRP channels in vascular cells may be hindered by the complex molecular biology of the superfamily. Biophysical properties of TRP channels have been investigated in patch-clamp experiments employing cultured cells expressing cloned TRP subunit genes. Under these conditions, most functional channels assemble from four identical TRP subunits. However, when multiple TRP subunits are coexpressed, assembly of tetramers composed of two or more TRP subunit proteins can form heteromeric channels [5,6] with novel properties [7,8]. Because most cells express multiple TRP subunits, it is likely that heteromeric channels exist in vivo. Furthermore, splice variants of TRP mRNAs in smooth muscle have been reported [9], potentially increasing the number of individual subunits available for coassembly. Because TRP molecular variety could result in an assortment of channels with a wide array of functional properties in native cells, unraveling the physiological consequences of TRP channel diversity presents a major challenge. In the following paragraphs, evidence for the presence and possible functional roles of TRP channels in vascular smooth muscle and endothelial cells are discussed.

Transient receptor potential (TRP) channels in the Manila clam (Ruditapes philippinarum): Characterization and expression patterns of the TRP gene family under heat stress in Manila clams based on genome-wide identification

Chapter 7 TRP Channels as Thermosensors

Phylogenetic analysis, tissue expression, and response to temperature variation of TRP genes in Monopterus albus.

XPORT-Dependent Transport of TRP and Rhodopsin

Background: Human NET cells express numerous of ion channel types. So far, voltage-dependend Ca2+ channels (all subtypes), sodium-, and potassium channels were described. Recently, chloride channels were detected (unpublished observation). In addition to these selective ion channels, non-selective TRP channels were also registered. These channels could be activated by active or passive store depletion or artificially by extracellular stimulation such as G-protein coupled receptor activation. Generally, channel activation will induce an increase of intracellular free Ca2+ concentration ([Ca2+]i). However, the physiological role of these ion channels in NET cells is absolutely unclear. Aim: Study of the electrophysiological properties of TRP channels by patch-clamp technique and fura-2 measurements in order to characterize the relevance of TRPs in the NE system more closely. Methods: Permanent NET BON cells were used as a representative cell model for NET diseases and were cultured according to established methods. In parallel, freshly isolated primary NET cells from several patients were cultured and also investigated. The TRP channel activities were measured by patch-clamp technique. [Ca2+]i was registered with the fluorescent dye fura-2. Furthermore, real-time PCR was used. Results: TRP channel activity of the M8 subtype (TRPM8) could be detected using the cooling agents menthol or icilin. As a result, Ca2+ influx was at higher levels than without activation of these channels. Furthermore, Ca2+ influx could also be registered after induction of oxidative stress by hydrogen peroxide (1 mM H2O2). This effect could be due to activation of the M7 subtype (TRPM7). Importantly, nickel-sensitive TRP-channel activity could additionally be detected in BON cells by induction of capacitative Ca2+ entry (CCE) after passive store depletion with 10µM cyclopiazonic acid (CPA). In the presence of 1 mM NiCl2, the CCE amplitude (set to 100%) decreased by 60±4% (recovery occurred to 78±3%) (±SEM; all n=3). Conclusion: For the first time, TRP channel expression of the M-family in NET cells could be demonstrated by several methods. TRPs could have an important role in the NE system. Specific intracellular TRP channel modulators (e.g. bioactive lipids) could exist. However, further investigation about expression and function of TRPs in NET cells are necessary.

Peritumoral brain edema (PTBE) has been widely reported with many brain tumors, especially with glioma. Since the blood-brain barrier (BBB) is essential for maintaining minimal permeability, any alteration in the interaction of BBB components, specifically in astrocytes and tight junctions (TJ), can result in disrupting the homeostasis of the BBB and making it severely leaky, which subsequently generates edema. This study aimed to evaluate the functional gliovascular unit of the BBB by examining changes in the expression of claudin (CLDN) genes and the expression of transient receptor potential (TRP) membrane channels, additionally to define the correlation between their expressions. The evaluation was conducted using invitro spheroid swelling models and tumor samples from glioma patients with PTBE. The results of the spheroid model showed that the genes TRPC3, TRPC4, TRPC5, and TRPV1 were upregulated in glioma cells either wild-type isocitrate dehydrogenase 1 (IDH1) or the IDH1 R132H mutant, with or without NaCl treatment. Furthermore, TRP genes appeared to adversely correlate with the up regulation of CLDN1, CLDN3, and CLDN5 genes. Besides, the upregulation of TRPC1 and TRPC4 in IDH1mt-R132H glioma cells. On the other hand, the correlation analysis revealed different correlations between different proteins in PTBE. CLDN1 exhibits a slight positive correlation with CLDN3. Similarly, TRPV1 displays a slight positive correlation with TRPC1. In contrast, TRPC4 shows a slight negative correlation with TRPC5. On the other hand, TRPC3 demonstrates a slight positive correlation with TRPC5, while the non-PTBE analysis highlights a moderate positive correlation between CLDN1 and TRPM4 while CLDN3 exhibits a moderate negative correlation with TRPC4. Additionally, CLDN5 demonstrates a slight negative correlation with TRPC4 but a moderate positive correlation with TRPC3. Furthermore, TRPC1 have a slight negative correlation with TRPV1, TRPC3 exhibiting a slight positive correlation with TRPC4, and TRPV1 showing a slight negative correlation with TRPC5. As a conclusion, the current study provided evidence of a slight negative correlation between TRPs and CLDN gene expression in PTBE patients and confirmatory results with some of the genes in cell model of edema.