TRPV2

Last updated
TRPV2
Protein TRPV2 PDB 2f37.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TRPV2 , VRL, VRL-1, VRL1, transient receptor potential cation channel subfamily V member 2
External IDs OMIM: 606676 MGI: 1341836 HomoloGene: 7993 GeneCards: TRPV2
Orthologs
SpeciesHumanMouse
Entrez

51393

22368

Ensembl

ENSG00000187688

ENSMUSG00000018507

UniProt

Q9Y5S1

Q9WTR1

RefSeq (mRNA)

NM_016113

NM_011706
NM_001382489
NM_001382490
NM_001382491
NM_001382492

Contents

RefSeq (protein)

NP_057197

NP_035836
NP_001369418
NP_001369419
NP_001369420
NP_001369421

Location (UCSC) Chr 17: 16.42 – 16.44 Mb Chr 11: 62.47 – 62.49 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transient receptor potential cation channel subfamily V member 2 is a protein that in humans is encoded by the TRPV2 gene. [5] [6] TRPV2 is a nonspecific cation channel that is a part of the TRP channel family. This channel allows the cell to communicate with its extracellular environment through the transfer of ions, and responds to noxious temperatures greater than 52 °C. It has a structure similar to that of potassium channels, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.

TRP subfamily

The vanilloid TRP subfamily (TRPV) named after the vanilloid receptor 1 consist of six members, four of them (TRPV1-TRPV4) have been related to thermal sensation. TRPV2 shares 50% of its homology with TRPV1. Compared to TRPV1 channels, TRPV2 channels do not open in response to vanilloids like capsaicin or thermal stimuli around 43 °C. [7] This may be due to the composition of the ankyrin repeat domains in TRPV2, which are different than those in TRPV1. However, TRPV2 channels can open by noxious temperatures greater than 52 °C. [7] TRPV2 initially was characterized as a noxious heat sensor channel, but more evidence suggest its importance in various osmosensory and mechanosensory mechanisms. The channel can open in response to a variety of stimuli including hormones, growth factors, mechanical stretching, heat, osmotic swelling, lysophospholipids, and cannabinoids. These channels are expressed in medium to large diameter neurons, motor neurons, and other non-neuronal tissues like the heart and lungs, which indicates its versatile function. The channel has an important role for basic cell function including contraction, cell proliferation, and cell death. The same channel can have different functions depending on the type of tissue. Other roles of TRPV2 continue to be explored in an attempt to define the role of translocation of TRPV2 by growth factors. SET2 is a TRPV2 selective antagonist. [8]

Discovery

TRPV2 was independently discovered by two research groups and described in 1999. It was identified in the lab of David Julius as a close homolog of TRPV1, known as the first identified thermosensitive ion channel. [5] Itaru Kojima from Gunma University was looking for a protein which is responsible for the entry of calcium into cells in response to insulin-like growth factor-1 (IGF-1). Upon stimulation of cells with IGF-1, it was discovered that TRPV2 translocates towards and integrates into the cell membrane and increases intracellular calcium concentrations.

Structure

TRPV2 channel has a similar structure to potassium channels, which are the largest ion channel family. This channel is composed of six transmembrane spanning regions (S1-S6) with a pore forming loop between S5 and S6. [9] The pore forming loop also defines the selectivity filter, which determines the ions that are able to enter the channel. The S1-S4 region, as well as the N and C terminals of the protein, is important in reference to the gating of the channel. Although TRPV2 is a nonspecific cation channel, it is more permeable to calcium ions; calcium is an intracellular messenger and plays a very important role in a variety of different cellular processes. At rest, the pore channel is closed; in the activated state, the channel opens, allowing the influx of sodium and calcium ions that initiates an action potential.

Species homology

Orthologoues between rat and mouse aligned with humans Orthologues of rats, mice, and humans.jpg
Orthologoues between rat and mouse aligned with humans

The TRPV subfamily of channels of 1 through 4 have unique functions. One important variation is that these channels trigger cellular signaling pathways via non-selective cation flux, making them unique. Specifically, the TRPV2 channel has structural similarities amongst the other members of the TRPV family. For instance, the channel consists of six transmembrane domains and a pore forming loop between S5 and S6. [9] Within the human genome, putative homologs can be found. This suggests that the amino acids and proteins coded come from a common ancestor where their structures are conserved in function.

Among the subfamily, TRPV2 and TRPV1 share 50% of their sequence identity not only in humans, but in rats as well. The rat TRPV2 can be comparable to that of humans because they exhibit similar surface localization among one another. Each channel possesses ATP binding regions and the 50% sequence identity between TRPV1 and TRPV2 suggests that both channel's Ankyrin repeat domain (ARD) bind to different regulatory ligands as well. [9] The channels structure can be observed as similar to that of potassium channels. In knockout mice, the physiological thermal responses show similar activation to wild-type mice. On top of that, humans, rats, and mice are considered orthologues.

Tissue distribution

Homo sapiens

In homo sapiens, there is broad expression of TRPV2 in the lymph nodes, spleen, lung, appendix, and placenta; it is mostly expressed in the lungs. [10] TRPV2 is majorly in a sub population of medium to large sensory neurons, as well as being distributed in the brain and spinal cord. [11] The mRNA expression of TRPV2 is also found in human pulmonary and umbilical vein endothelial cells. [11] Based on mRNA expression of TRPV2 in mice, it is also speculated that it is expressed in arterial muscle cells, which can then be influenced by blood pressure; though it was evident that TRPV2 expression was localized in the intracellular area, some growth factors localized it to the plasma cell membrane. [11] In circulatory organs, studies and data suggest that TRPV2 may be a mechanosensor, meaning that it can sense changes in external stimuli; the mechanisms involved in opening TRPV2 by membrane stretching or hypoosmotic cell swelling have not yet been determined. [11]

Mus musculus

Mus Musculus-huismuis2 Mus Musculus-huismuis2.jpg
Mus Musculus-huismuis2

In mus musculus (house mouse), TRPV2 functions as a protein coding gene. There is broad expression of TRPV2 in the thymus, placenta, cerebellum, and spleen; it is most commonly expressed in the thymus. [12] The thymus is a lymphoid organ involved in the function of the immune system, where T cells mature. T cells are an important component to the adaptive immune system, because it is where the body adapts to foreign substances; this demonstrates TRPV2's importance in the immune system. TRPV2 in mus musculus is also activated by hypo-osmolarity and cell stretching, indicating that TRPV2 plays a role in mechanotransduction in mice as well. [12] In experiments with knockout mice (TRPV2KO mice), it was found that TRPV2 is expressed in brown adipocytes and in brown adipose tissue (BAT). It can be concluded that TRPV2 plays a role in BAT thermogenesis in mice, since it was found that a lack of TRPV2 impairs this thermogenesis in BAT; given these results, this could be a target for human obesity therapy. [13]

Rattus norvegicus

In rattus norvegicus (Norway rat), there is broad expression of TRPV2 in the adrenal glands and the lungs, being most present in the adrenal glands. TRPV2 is also present in the thymus and spleen, but not in high amounts. Without using any external growth factors, TRPV2 is highly specific to the plasma cell membrane in rat adult dorsal root ganglions, cerebral cortex, and arterial muscle cells. [11]

Clinical significance

Cancer

TRPV2 plays a role in negative homeostatic control of excess cell proliferation by inducing apoptosis (programmed cell death). [9] This is accomplished predominantly through the Fas pathway, also known as the death-inducing signaling complex. Activation of TRPV2 by growth factors and hormones induces the receptor to translocate from intracellular compartments to the plasma membrane, which initiates the development of death signals. [14] An example of the role of TRPV2 in apoptosis is its expression in the bladder cancer t24 cell line. TRPV2 in bladder cancer leads to apoptosis through the influx of calcium ions through the TPRV2 channel. In some tumors, the over-expression of TRPV2 can lead to abnormal signaling pathways that drives unchecked cell proliferation and resistance to apoptotic stimuli. The over-expression of TRPV2 has been linked to several cancer types and cell lines. [15] [16] TRPV2 is expressed in human HepG2 cells, a cell line containing human liver carcinogenic cells. Heat allows for calcium entry into these cells through TRPV2 channels, which aid in the maintenance of these cells. [17] TRPV2 also negatively affects patients with gliomas. TRPV2 in carcinogenic glial cells leads to resistance to apoptotic cell death, leading to harmful, carcinogenic cell survival. [18]

Immunity

Antigens presentation Antigens presentation.svg
Antigens presentation

TRPV2 is expressed in the spleen, lymphocytes, and myeloid cells including granulocytes, macrophages and mast cells. Among these cell types, TRPV2 mediates cytokine release, phagocytosis, endocytosis, podosome assembly, and inflammation. [19] The influx of calcium seems to play an important role in these functions. Mast cells are leukocytes (white blood cells) rich in histamine which are able to respond to a variety of stimuli, often initiating inflammatory and/or allergic responses. The responses generated by mast cells rely on the calcium influx in the plasma membrane with the help of channels. Surface localization of the TRPV2 protein along with coupling of the protein to calcium and proinflammatory degranulation have been found in mast cells. The activation of TRPV2 in high temperatures permits calcium ion influx, inducing the release of proinflammatory factors. Therefore, TRPV2 is essential in mast cell degranulation as a result of its response to heat. [20] Immune cells are also able to kill pathogens by binding to them and engulfing them in a process known as phagocytosis. In macrophages TRPV2 recruitment toward the phagosome is regulated by PI3k signaling, protein kinase C, akt kinase, and Src kinases. [9] They are able to locate these microbes through chemotaxis which is TRPV2 mediated. When the pathogen is endocytosed it is degraded then presented on the membrane of antigen presenting cells (i.e. macrophages). Macrophages present these antigens to T cells via a major histocompatibility complex (MHC). The region between the MHC-peptide and the T cell receptor is known as the immunosynapse. TRPV2 channels are highly concentrated in this region. When these two cells interact, it allows calcium to diffuse through the TRPV2 channel. TRPV2 mRNA has been detected in CD4+ and CD8+ T cells as well as in human B lymphocytes. TRPV2 is one type of ion channel that directs T cell activation, proliferation, and defense mechanisms. If the TRPV2 channel were absent or not functioning properly in T cells, T cell receptor signaling would not be optimal. TRPV2 also acts as a transmembrane protein on the surface of B cells, negatively controlling B cell activation. [20] Abnormal TRPV2 expression has been reported in hematological diseases including multiple myeloma, myelodysplastic syndrome, Burkitt lymphoma, and acute myeloid leukemia. [19]

Metabolic

TRPV2 seems to be essential in glucose homeostasis. It is highly expressed in MIN6 cells, which is a β-cell. These cell types are known for releasing insulin, a molecule that functions to keep glucose levels low. Under unstimulated conditions, TRPV2 is localized in the cytoplasm. Activation causes the channel to translocate to the plasma membrane. This triggers the influx of calcium resulting in insulin secretion. [7]

Cardiovascular

TRPV2 is very important in the structure and function of cardiomyocytes (heart cells). Compared to skeletal muscles, TRPV2 is expressed 10 times as high in cardiomyocytes [21] and is important in current conduction. TRPV2 has been shown to be involved in stretch-dependent responses in heart cells. TRPV2 expression is concentrated in intercalated discs which allows the synchronous contraction of cardiomyocytes. Abnormal expression of TRPV2 results in reduced shortening length, shortening rate, and lengthening rate which ultimately compromise cardiac contractile function.

Ligands

Agonist

Agonists include: [22]

See also

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

<span class="mw-page-title-main">TRPV6</span> Protein-coding gene in the species Homo sapiens

TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.

<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. And a receptor being clearly present in bacteria, the oldest organisms on Earth known to express phosphatidylethanolamine, the precursor to endocannabinoids, in their cytoplasmic membranes, and fatty acid metabolites with affinity for this CB receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA).

TRPC is a family of transient receptor potential cation channels in animals.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

TRPM is a family of transient receptor potential ion channels (M standing for wikt:melastatin). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8.

<span class="mw-page-title-main">MCOLN1</span> Protein-coding gene in the species Homo sapiens

Mucolipin-1 also known as TRPML1 is a protein that in humans is encoded by the MCOLN1 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.

<span class="mw-page-title-main">TRPM2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

<span class="mw-page-title-main">TRPA1</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the TRPA1 gene.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

<span class="mw-page-title-main">TRPM4</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 4 (hTRPM4), also known as melastatin-4, is a protein that in humans is encoded by the TRPM4 gene.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

<span class="mw-page-title-main">TRPV3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human gene encoding the protein of the same name.

<span class="mw-page-title-main">TRPM7</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7, is a human gene encoding a protein of the same name.

<span class="mw-page-title-main">TRPV5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the TRPV5 gene.

<span class="mw-page-title-main">Iodoresiniferatoxin</span> Chemical compound

Iodoresiniferatoxin (I-RTX) is a strong competitive antagonist of the Transient Receptor Potential Vanilloid 1 (TRPV1) receptor. I-RTX is derived from resiniferatoxin (RTX).

Relief from chronic pain remains a recognized unmet medical need. Consequently, the search for new analgesic agents is being intensively studied by the pharmaceutical industry. The TRPV1 receptor is a ligand gated ion channel that has been implicated in mediation of many types of pain and therefore studied most extensively. The first competitive antagonist, capsazepine, was first described in 1990; since then, several TRPV1 antagonists have entered clinical trials as analgesic agents. Should these new chemical entities relieve symptoms of chronic pain, then this class of compounds may offer one of the first novel mechanisms for the treatment of pain in many years.

The transient receptor potential Ca2+ channel (TRP-CC) family (TC# 1.A.4) is a member of the voltage-gated ion channel (VIC) superfamily and consists of cation channels conserved from worms to humans. The TRP-CC family also consists of seven subfamilies (TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML) based on their amino acid sequence homology:

  1. the canonical or classic TRPs,
  2. the vanilloid receptor TRPs,
  3. the melastatin or long TRPs,
  4. ankyrin (whose only member is the transmembrane protein 1 [TRPA1])
  5. TRPN after the nonmechanoreceptor potential C (nonpC), and the more distant cousins,
  6. the polycystins
  7. and mucolipins.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000187688 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018507 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (April 1999). "A capsaicin-receptor homologue with a high threshold for noxious heat". Nature. 398 (6726): 436–41. Bibcode:1999Natur.398..436C. doi: 10.1038/18906 . PMID   10201375. S2CID   4415522.
  6. ↑ Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID   16382100. S2CID   17936350.
  7. 1 2 3 Shibasaki K (September 2016). "Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor". The Journal of Physiological Sciences. 66 (5): 359–65. doi: 10.1007/s12576-016-0434-7 . PMID   26841959. S2CID   582291.
  8. ↑ Chai H, Cheng X, Zhou B, Zhao L, Lin X, Huang D, et al. (February 2019). "Structure-Based Discovery of a Subtype-Selective Inhibitor Targeting a Transient Receptor Potential Vanilloid Channel". Journal of Medicinal Chemistry. 62 (3): 1373–1384. doi:10.1021/acs.jmedchem.8b01496. PMID   30620187. S2CID   58543255.
  9. 1 2 3 4 5 Perálvarez-Marín A, Doñate-Macian P, Gaudet R (November 2013). "What do we know about the transient receptor potential vanilloid 2 (TRPV2) ion channel?" (PDF). The FEBS Journal. 280 (21): 5471–87. doi:10.1111/febs.12302. PMC   3783526 . PMID   23615321.
  10. ↑ "TRPV2: transient receptor potential cation channel subfamily V member 2 [Homo sapiens (human)]". NCBI.
  11. 1 2 3 4 5 Katsuhiko M, Shigekawa M, Imaizumi Y (2007). "Chapter 28A: New Insight into the Function of TRPV2 in Circulatory Organs". In Liedtke WB, Heller S (eds.). TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Frontiers in Neuroscience. Boca Raton (FL): CRC Press/Taylor & Francis. ISBN   978-0-8493-4048-2.
  12. 1 2 "TRPV2: transient receptor potential cation channel, subfamily V, member 2 [Mus musculus (house mouse)]". NCBI. NCBI.
  13. ↑ Sun W, Uchida K, Suzuki Y, Zhou Y, Kim M, Takayama Y, et al. (March 2016). "Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue". EMBO Reports. 17 (3): 383–99. doi:10.15252/embr.201540819. PMC   4772987 . PMID   26882545.
  14. ↑ Liberati S, Morelli MB, Amantini C, Santoni M, Nabissi M, Cardinali C, Santoni G (2014). "Advances in transient receptor potential vanilloid-2 channel expression and function in tumor growth and progression". Current Protein & Peptide Science. 15 (7): 732–7. doi:10.2174/1389203715666140704115913. hdl:11581/359381. PMID   25001513.
  15. ↑ Santoni G, Amantini C, Maggi F, Marinelli O, Santoni M, Nabissi M, Morelli MB (February 2020). "The TRPV2 cation channels: from urothelial cancer invasiveness to glioblastoma multiforme interactome signature". Laboratory Investigation; A Journal of Technical Methods and Pathology. 100 (2): 186–198. doi: 10.1038/s41374-019-0333-7 . PMID   31653969. S2CID   204887121.
  16. ↑ Siveen KS, Nizamuddin PB, Uddin S, Al-Thani M, Frenneaux MP, Janahi IA, et al. (2020). "TRPV2: A Cancer Biomarker and Potential Therapeutic Target". Disease Markers. 2020: 8892312. doi: 10.1155/2020/8892312 . PMC   7746447 . PMID   33376561.
  17. ↑ Lehen'kyi V, Prevarskaya. "TRPV2 (transient potential cation channel, subfamily V, member 2)". Atlas of Genetics and Cytogenetic in Oncology and Haematology.
  18. ↑ Nabissi M, Morelli MB, Amantini C, Farfariello V, Ricci-Vitiani L, Caprodossi S, et al. (May 2010). "TRPV2 channel negatively controls glioma cell proliferation and resistance to Fas-induced apoptosis in ERK-dependent manner". Carcinogenesis. 31 (5): 794–803. doi: 10.1093/carcin/bgq019 . PMID   20093382.
  19. 1 2 Caterina MJ, Pang Z (December 2016). "TRP Channels in Skin Biology and Pathophysiology". Pharmaceuticals. 9 (4): 77. doi: 10.3390/ph9040077 . PMC   5198052 . PMID   27983625.
  20. 1 2 Santoni G, Farfariello V, Liberati S, Morelli MB, Nabissi M, Santoni M, Amantini C (2013-02-14). "The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses". Frontiers in Immunology. 4: 34. doi: 10.3389/fimmu.2013.00034 . PMC   3572502 . PMID   23420671.
  21. ↑ Aguettaz E, Bois P, Cognard C, Sebille S (November 2017). "Stretch-activated TRPV2 channels: Role in mediating cardiopathies". Progress in Biophysics and Molecular Biology. 130 (Pt B): 273–280. doi:10.1016/j.pbiomolbio.2017.05.007. PMID   28546113.
  22. ↑ Muller C, Morales P, Reggio PH (2019-01-15). "Cannabinoid Ligands Targeting TRP Channels". Frontiers in Molecular Neuroscience. 11: 487. doi: 10.3389/fnmol.2018.00487 . PMC   6340993 . PMID   30697147.
  23. ↑ Laragione T, Harris C, Gulko PS. Combination therapy of a TRPV2 agonist with a TNF inhibitor achieves sustained suppression of disease severity and reduced joint damage. Clin Exp Immunol. 2023 Mar 24;211(3):233-238. doi : 10.1093/cei/uxac124 PMID   36571199

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.