Transient Receptor Potential Family Research Articles

Protective Effect of Transient Receptor Potential Ankyrin 1 Inhibition on Renal Ischemia Reperfusion Injury in Rats.

The transient receptor potential ankyrin 1 (TRPA1) channels, characterized as nonselective cation channels with permeability to calcium ions (Ca2 +), are part of the extensive family of transient receptor potential (TRP) channels. Research has demonstrated that TRPA1 channels function as sensors for oxidative stress in the renal tubules. Additionally, TRPA1 expression has increased in renal tissue following ischemia-reperfusion (IR). There is also a significant correlation between IR-induced renal injury and TRPA1 expression. This study investigated the effects of selective TRPA1 agonist ASP7663 and selective TRPA1 antagonist HC-030031 on renal IR injury. A total of 40 rats were divided into four groups: control, IR, IR+ASP7663, and IR + HC-030031. The rat kidneys were exposed to 45 min of ischemia, followed by 24 h of reperfusion. TRPA1 agonist ASP7663 and selective TRPA1 antagonist HC-030031 were administered intraperitoneally to the treatment groups with renal IR. HC-030031 administration reduced the elevated kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cre) caused by renal IR. HC-030031 administration reduced the increased histopathological damage in renal tissue due to IR. It also reduced renal tissue interleukin-1beta (IL-1β), interleukin-6 (IL-6), toll-like receptor-4 (TLR-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor-alpha (TNF-α), and caspase-3 levels. In this study, TRPA1 antagonist HC-030031 showed a protective behavior on renal IR injury by averting inflammation and apoptosis. After further studies, TRPA1 inhibition may be a new treatment strategy to prevent renal IR injury.

Protein dynamics underlies strong temperature dependence of heat receptors

Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals. Despite intensive studies, however, the nature of the temperature sensor domain in these channels remains elusive. By direct calorimetry of TRPV1 proteins, we have recently provided a proof of principle that temperature sensing by ion channels may diverge from the conventional allosterity theory; rather it is intimately linked to inherent thermal instability of channel proteins. Here, we tackle the generality of the hypothesis and provide key molecular pieces of evidence on the coupling of thermal transitions in the channels. We show that while wild-type channels possess a single concerted thermal transition peak, the chimera, in which strong temperature dependence becomes disrupted, results in multitransition peaks, and the activation enthalpies are accordingly reduced. The data show that the coupling with protein unfolding drives up the energy barrier of activation, leading to a strong temperature dependence of opening. Furthermore, we pinpoint the proximal N-terminus of the channels as a linchpin in coalescing different parts of the channels into concerted activation. Thus, we suggest that coupled interaction networks in proteins underlie the strong temperature dependence of temperature receptors.

The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chondrichthyans: chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

Generation of two isogenic human iPSC lines (ZIPi013-B-1, ZIPi013-B-2) carrying a CRISPR/Cas9-mediated deletion of TRPM4

Two isogenic hiPSC lines, ZIPi013-B-1 and ZIPi013-B-2, were generated by CRISPR/Cas9-mediated indels in the TRPM4 gene of the previously published ZIPi013-B. TRPM4 belongs to the evolutionarily conserved family of transient receptor potential (TRP) channels. It is expressed ubiquitously and its activity is regulated by intracellular calcium binding, changes in membrane potential, phosphoinositide lipids in the plasma membrane and the local concentration of cytoplasmic ATP and ADP. TRPM4 has been implicated in various diseases, including neurological and immune system disorders, cardiac diseases and cancer. Both new cell lines offer the opportunity to model human diseases and test therapeutic modalities addressing these.

The Interaction Mechanism Between C14-Polyacetylene Compounds and the Rat TRPA1 Receptor: An In Silico Study.

Polyacetylene (PA) compounds, as natural products, exhibit remarkable properties and distinctive chemical activities. Three structurally similar C14-PA compounds-Echinophorin D, Echinophorin B, and Echinophorin A-extracted from plants demonstrate varying biological activities on the Transient Receptor Potential Channel A1 (TRPA1) protein, which belongs to the TRP (Transient Receptor Potential) family. In the current study, we investigated the binding modes of these three PA compounds with TRPA1 using molecular dynamics (MD), molecular docking, binding free energy calculations, and quantum mechanics/molecular mechanics (QM/MM) methods. Initially, a putative binding site (site-II) in TRPA1 was identified for these compounds; Echinophorin B was found to stabilize the upward A-loop of TRPA1, which is critical for its activation. Furthermore, the binding affinity calculations of PA compounds through molecular fragment decomposition indicate that the arrangement of two triple bonds and one double bond in C14-PA compounds is vital for regulating TRPA1 bioactivity. Additionally, the lipophilic and electronic properties of the three molecules were analyzed in relation to binding affinity, establishing a correlation between TRPA1 activity and these molecular properties.

Functions of TRPs in retinal tissue in physiological and pathological conditions.

The Transient Receptor Potential (TRP) constitutes a family of channels subdivided into seven subfamilies: Ankyrin (TRPA), Canonical (TRPC), Melastatin (TRPM), Mucolipin (TRPML), no-mechano-potential C (TRPN), Polycystic (TRPP), and Vanilloid (TRPV). Although they are structurally similar to one another, the peculiarities of each subfamily are key to the response to stimuli and the signaling pathway that each one triggers. TRPs are non-selective cation channels, most of which are permeable to Ca2+, which is a well-established second messenger that modulates several intracellular signaling pathways and is involved in physiological and pathological conditions in various cell types. TRPs depolarize excitable cells by increasing the influx of Ca2+, Na+, and other cations. Most TRP families are activated by temperature variations, membrane stretching, or chemical agents and, therefore, are defined as polymodal channels. All TPRs are expressed, at some level, in the central nervous system (CNS) and ocular-related structures, such as the retina and optic nerve (ON), except the TRPP in the ON. TRPC, TRPM, TRPV, and TRPML are found in the retinal pigmented cells, whereas only TRPA1 and TRPM are detected in the uvea. Accordingly, several studies have focused on the search to unravel the role of TRPs in physiological and pathological conditions related to the eyes. Thus, this review aims to shed light on endogenous and exogenous modulators, triggered cell signaling pathways, and localization and roles of each subfamily of TRP channels in physiological and pathological conditions in the retina, optic nerve, and retinal pigmented epithelium of vertebrates.

Genome-wide identification, characterization, and expression analysis of the transient receptor potential gene family in mandarin fish Siniperca chuatsi

BackgroundTemperature is a crucial environmental determinant for the vitality and development of teleost fish, yet the underlying mechanisms by which they sense temperature fluctuations remain largely unexplored. Transient receptor potential (TRP) proteins, renowned for their involvement in temperature sensing, have not been characterized in teleost fish, especially regarding their temperature-sensing capabilities.ResultsIn this study, a genome-wide analysis was conducted, identifying a total of 28 TRP genes in the mandarin fish Siniperca chuatsi. These genes were categorized into the families of TRPA, TRPC, TRPP, TRPM, TRPML, and TRPV. Despite notable variations in conserved motifs across different subfamilies, TRP family members shared common structural features, including ankyrin repeats and the TRP domain. Tissue expression analysis showed that each of these TRP genes exhibited a unique expression pattern. Furthermore, examination of the tissue expression patterns of ten selected TRP genes following exposure to both high and low temperature stress indicated the expression of TRP genes were responsive to temperatures changes. Moreover, the expression profiles of TRP genes in response to mandarin fish virus infections showed significant upregulation for most genes after Siniperca chuatsi rhabdovirus, mandarin fish iridovirus and infectious spleen and kidney necrosis virus infection.ConclusionsThis study characterized the TRP family genes in mandarin fish genome-wide, and explored their expression patterns in response to temperature stress and virus infections. Our work will enhance the overall understanding of fish TRP channels and their possible functions.

Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.

Electrical cell‐substrate impedance sensing (ECIS) in lung biology and disease

AbstractThe lungs are exposed to a hostile environment from both sites: the airways and the vasculature. However, an efficient gas exchange of oxygen (O2) and CO2 is only possible through a very thin alveolo‐capillary membrane. Therefore, maintaining cell barrier integrity is essential for respiratory health and function. On the vascular site, endothelial cells form a natural barrier, while in the airways epithelial cells are most important for protection of the lung tissues. Moreover, fibroblasts, by transforming to myofibroblasts, are essential for wound closure after mechanical and chemical microinjuries in the respiratory tract. Along this line, loss of cell resistance in vascular endothelial and lung epithelial cells enhances invasion of pathogens (e.g., SARS‐CoV‐2) and results in pulmonary edema formation, while increasing barrier function of pulmonary (myo)fibroblasts blocks gas exchange in patients with pulmonary fibrosis. Therefore, electrical cell‐substrate impedance sensing‐based quantification of changes in cell barrier function in lung endothelial and epithelial cells as well as fibroblasts after application of harmful triggers (e.g., hypoxia, receptor agonists, and toxicants) is a convenient and state‐of‐the‐art technique. After isolation of primary cells from mouse models and human tissues, changes in cell resistance can be detected in real time. By using lung cells from gene‐deficient mouse models, microRNAs or the small‐interfering RNA technology essential proteins for cell adhesion, for example, ion channels of the transient receptor potential family are identified in comparison to wild‐type control cells. In the future, these proteins may be useful as drug targets for novel therapeutic options in patients with lung edema or pulmonary fibrosis.

Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.

Conventional gene therapy approaches for drug delivery generally rely on constitutive expression of the transgene and thus lack precise control over the timing and magnitude of delivery. Synthetic gene circuits with promoters that are responsive to user-defined stimuli can provide a molecular switch that can be utilized by cells to control drug production. Our laboratory has previously developed a mechanogenetic gene circuit that can deliver biological drugs, such as interleukin-1 receptor antagonist (IL-1Ra), on-demand through the activation of Transient receptor potential family, vanilloid 4 (TRPV4), a mechanosensory ion channel that has been shown to be activated transiently in response to physical stimuli such as physiological mechanical loading or hypo-osmotic stimuli. The goal of this study was to use mutations in TRPV4 to further tune the response of this mechanogenetic gene circuit. Human iPSC-derived chondrocytes harboring targeted gain-of-function mutations of TRPV4 were chondrogenically differentiated. Both mutants-V620I and T89I-showed greater total IL-1Ra production compared with wild type following TRPV4 agonist treatment, as well as mechanical or osmotic loading, but with altered temporal dynamics. Gene circuit output was dependent on the degree of TRPV4 activation secondary to GSK101 concentration or strain magnitude during loading. V620I constructs secreted more IL-1Ra compared with T89I across all experimental conditions, indicating that two mutations that cause similar functional changes to TRPV4 can result in distinct circuit activation profiles that differ from wild-type cells. In summary, we successfully demonstrate proof-of-concept that point mutations in TRPV4 that alter channel function can be used to tune the therapeutic output of mechanogenetic gene circuits.

The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

New perspectives in prognostication of hepatocellular carcinoma: The role and clinical implications of transient receptor potential family genes.

The study titled "Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients" is a significant contribution to hepatocellular carcinoma (HCC) research, highlighting the role of transient receptor potential (TRP) family genes in the disease's progression and prognosis. Utilizing data from The Cancer Genome Atlas database, it establishes a new risk assessment model, emphasizing the interaction of TRP genes with tumor proliferation pathways, key metabolic reactions like retinol metabolism, and the tumor immune microenvironment. Notably, the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes, suggesting its potential as a prognostic biomarker and a target for personalized therapy, particularly in strategies combining immunotherapy and anti-TRP agents.

Function and mechanism of action of the TRPV1 channel in the development of triple-negative breast cancer.

Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.

The mechanisms of exercise improving cardiovascular function by stimulating Piezo1 and TRP ion channels: a systemic review.

Mechanosensitive ion channels are widely distributed in the heart, lung, bladder and other tissues, and plays an important role in exercise-induced cardiovascular function promotion. By reviewing the PubMed databases, the results were summarized using the terms "Exercise/Sport", "Piezo1", "Transient receptor potential (TRP)" and "Cardiovascular" as the keywords, 124-related papers screened were sorted and reviewed. The results showed that: (1) Piezo1 and TRP channels play an important role in regulating blood pressure and the development of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cardiac fibrosis; (2) Exercise promotes cardiac health, inhibits the development of pathological heart to heart failure, regulating the changes in the characterization of Piezo1 and TRP channels; (3) Piezo1 activates downstream signaling pathways with very broad pathways, such as AKT/eNOS, NF-κB, p38MAPK and HIPPO-YAP signaling pathways. Piezo1 and Irisin regulate nuclear localization of YAP and are hypothesized to act synergistically to regulate tissue mechanical properties of the cardiovascular system and (4) The cardioprotective effects of exercise through the TRP family are mostly accomplished through Ca2+ and involve many signaling pathways. TRP channels exert their important cardioprotective effects by reducing the TRPC3-Nox2 complex and mediating Irisin-induced Ca2+ influx through TRPV4. It is proposed that exercise stimulates the mechanosensitive cation channel Piezo1 and TRP channels, which exerts cardioprotective effects. The activation of Piezo1 and TRP channels and their downstream targets to exert cardioprotective function by exercise may provide a theoretical basis for the prevention of cardiovascular diseases and the rehabilitation of clinical patients.

Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.

The large family of transient receptor potential (TRP) channels are integral membrane proteins that function as environmental sensors and act as ion channels after activation by mechanical (touch), physical (heat, pain), and chemical stimuli (pungent compounds such as capsaicin). Most TRP channels are localized in the plasma membrane of cells but some of them are localized in membranes of organelles and function as intracellular Ca2+-ion channels. TRP channels are involved in neurological disorders but their precise role(s) and relevance in these disorders are not clear. Endothelial cells of the blood-brain barrier (BBB) express TRP channels such as TRP vanilloid 1-4 and are involved in thermal detection by regulating BBB permeability. In neurological disorders, TRP channels in the BBB are responsible for edema formation in the brain. Therefore, drug design to modulate locally activity of TRP channels in the BBB is a hot topic. Today, the application of TRP channel antagonists against neurological disorders is still limited.

Phenolic acids from Chicory roots ameliorate dextran sulfate sodium–induced colitis in mice by targeting TRP signaling pathways and the gut microbiota

BackgroundInflammatory bowel disease (IBD) is a type of immune–mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti–inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in–depth investigation into the underlying mechanisms. MethodsOn the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. ResultsIt was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. ConclusionPA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.

Identification of transient receptor potential channel genes from the swimming crab, Portunus Trituberculatus, and their expression profiles under acute temperature stress

BackgroundTemperature is an important environment factor that is critical to the survival and growth of crustaceans. However, the mechanisms by which crustaceans detect changes in temperature are still unclear. The transient receptor potential (TRP) channels are non-selective cation channels well known for properties in temperature sensation. However, comprehensive understandings on TRP channels as well as their temperature sensing functions are still lacking in crustaceans.ResultsIn this study, a total of 26 TRP genes were identified in the swimming crab, Portunus trituberculatus, which can be classified into TRPA, TRPC, TRPP, TRPM, TRPML, TRPN and TRPV. Tissue expression analysis revealed a wide distribution of these TRP genes in P. trituberculatus, and antennules, neural tissues, and ovaries were the most commonly expressed tissues. To investigate the responsiveness of TRP genes to the temperature change, 18 TRPs were selected to detect their expression after high and low temperature stress. The results showed that 12 TRPs showed induced gene expression in both high and low temperature groups, while 3 were down-regulated in the low temperature group, and 3 showed no change in expression in either group.ConclusionsThis study characterized the TRP family genes in P. trituberculatus, and explored their involvement in response to temperature stress. Our results will enhance overall understanding of crustacean TRP channels and their possible functions.

Transcriptomic profile of the mechanosensitive ion channelome in human cardiac fibroblasts.

Human cardiac fibroblasts (HCFs) have mRNA transcripts that encode different mechanosensitive ion channels and channel regulatory proteins whose functions are not known yet. The primary goal of this work was to define the mechanosensitive ion channelome of HCFs. The most common type of cationic channel is the transient receptor potential (TRP) family, which is followed by the TWIK-related K+ channel (TREK), transmembrane protein 63 (TMEM63), and PIEZO channel (PIEZO) families. In the sodium-dependent NON-voltage-gated channel (SCNN) subfamily, only SCNN1D was shown to be highly expressed. Particular members of the acid-sensing ion channel (ASIC) (ASIC1 and ASIC3) subfamilies were also significantly expressed. The transcripts per kilobase million (TPMs) for Piezo 2 were almost 100 times less abundant than those for Piezo 1. The tandem of P domains in a weak inward rectifying K+ channel (TWIK)-2 channel, TWIK-related acid-sensitive K+ channel (TASK)-5, TASK-1, and the TWIK-related K1 (TREK-1) channel were the four most prevalent types in the K2P subfamily. The highest expression in the TRPP subfamily was found for PKD2 and PKD1, while in the TRPM subfamily, it was found for TRPM4, TRPM7, and TRPM3. TRPV2, TRPV4, TRPV3, and TRPV6 (all members of the TRPV subfamily) were also substantially expressed. A strong expression of the TRPC1, TRPC4, TRPC6, and TRPC2 channels and all members of the TRPML subfamily (MCOLN1, MCOLN2, and MCOLN3) was also shown. In terms of the transmembrane protein 16 (TMEM16) family, the HCFs demonstrated significant expression of the TMEM16H, TMEM16F, TMEM16J, TMEM16A, and TMEM16G channels. TMC3 is the most expressed channel in HCFs of all known members of the transmembrane channel-like protein (TMC) family. This analysis of the mechanosensitive ionic channel transcriptome in HCFs: (1) agrees with previously documented findings that all currently identified mechanosensitive channels play a significant and well recognized physiological function in elucidating the mechanosensitive characteristics of HCFs; (2) supports earlier preliminary reports that point to the most common expression of the TRP mechanosensitive family in HCFs; and (3) points to other new mechanosensitive channels (TRPC1, TRPC2, TWIK-2, TMEM16A, ASIC1, and ASIC3).

Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients.

Members of the transient receptor potential (TRP) protein family shape oncogenic development, but the specific relevance of TRP-related genes in hepatocellular carcinoma (HCC) has yet to be defined. To investigate the role of TRP genes in HCC, their association with HCC development and treatment was examined. HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database, and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum. Based on these analyses, clinically relevant TRP family genes were selected, and the association between the key TRP canonical type 1 (TRPC1) gene and HCC patient prognosis was evaluated. In total, 28 TRP family genes were screened for clinical relevance, with multivariate analyses ultimately revealing three of these genes (TRPC1, TRP cation channel subfamily M member 2, and TRP cation channel subfamily M member 6) to be significantly associated with HCC patient prognosis (P < 0.05). These genes were utilized to establish a TRP-related risk model. Patients were separated into low- and high-risk groups based on the expression of these genes, and high-risk patients exhibited a significantly poorer prognosis (P = 0.001). Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways. TRPC1 was identified as a candidate gene in this family worthy of further study, with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes. Consistently, quantitative, immunohistochemistry, and western blot analyses revealed increased TRPC1 expression in HCC. These three TRP genes help determine HCC patient prognosis, providing insight into tumor immune status and immunological composition. These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.

TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches.

Ion channels play a crucial role in a wide range of biological processes, including cell cycle regulation and cancer progression. In particular, the transient receptor potential (TRP) family of channels has emerged as a promising therapeutic target due to its involvement in several stages of cancer development and dissemination. TRP channels are expressed in a large variety of cells and tissues, and by increasing cation intracellular concentration, they monitor mechanical, thermal, and chemical stimuli under physiological and pathological conditions. Some members of the TRP superfamily, namely vanilloid (TRPV), canonical (TRPC), melastatin (TRPM), and ankyrin (TRPA), have been investigated in different types of cancer, including breast, prostate, lung, and colorectal cancer. TRP channels are involved in processes such as cell proliferation, migration, invasion, angiogenesis, and drug resistance, all related to cancer progression. Some TRP channels have been mechanistically associated with the signaling of cancer pain. Understanding the cellular and molecular mechanisms by which TRP channels influence cancer provides new opportunities for the development of targeted therapeutic strategies. Selective inhibitors of TRP channels are under initial scrutiny in experimental animals as potential anti-cancer agents. In-depth knowledge of these channels and their regulatory mechanisms may lead to new therapeutic strategies for cancer treatment, providing new perspectives for the development of effective targeted therapies.