TRPV2 Gene Editing    

Transient receptor potential vanilloid type 2 (TRPV2) is a calcium-permeable cation channel of TRPV family. Caterina et al. identified TRPV2 as vanilloid receptor-like protein-1 (VRL-1), which is a molecule structurally related to vanilloid receptor TRPV1. The expression level of TRPV2 varies with the type of tissues and cells. TRPV1 was highly expressed in sensory neurons, and pungent compounds such as capsaicin could evoke TRPV1 activation. In view of the burning qualities of capsaicin-induced pain, capsaicin and heat may evoke painful responses through a common molecular mechanism. It is speculated that TRPV1 can be activated by heat at >43 °C, a temperature threshold that is consistent with that of heat-evoked pain.

TRPV2 Modulation and Cardiac Function

In 2003, it was first reported the expression of TRPV2 channel, growth factor regulated channel (GRC), in cardiac cells. TRPV2 was found about 10-fold more abundant in cardiac than in skeletal muscle with a prominent expression in intercalated discs. Then, TRPV2 channels have been presented as molecular candidates for cardiac stretch-activated ion channels because their mechanosensitivity was characterized using cell volume changes and patch-pipette suction in aortic myocytes. TRPV2 was found at high concentrations and activated in three different animal models of DCM related to dystrophic diseases: the transgenic mice overexpressing sialytransferase, the d-sarcoglycan deficient hamsters, and also in the model of doxorubicin-induced DCM mice. In each model, sarcolemmal accumulation of TRPV2 was found to be significantly increased when compared to the Wild type. TRPC1 and TRPV2 expression was significantly higher in DCM than in control and TRPV2 was strongly detected at the peripheral sarcolemma of DCM cardiomyocytes. Compared with DCM tissue, in normal ventricles, TRPV2 localized to the intracellular compartments and intercalated discs, indicating the involvement of TRPV2 in the physiopathology of DCM.

TRPV2 Expression Profile Is Altered in Hematological Cancers

In immune cells, TRPV2 acts as a molecular sensor in diverse functions that include phagocytosis/degranulation, migration/chemotaxis, cytokine secretion, infiltration of tissues, cytokine release, endocytosis, inflammasome activity, neuroinflammation, and podosome assembly. In fact, circulating lymphocytes are affected by changes in fluid flow, osmolarity and blood pressure, shape during processes such as extravasation/infiltration of tissues, antigen recognition, and maturation/activation. TRPV2 can facilitate these processes because it is directly or indirectly gated by mechanical stretch. Loss, mutation or gain of the TRPV2 gene have been reported in hematological tumors, including mantle cell lymphoma, multiple myeloma, acute myeloid leukemia, Burkitt lymphoma, and myelodysplastic syndrome. Furthermore, TRPV2 expression in CD34+/CD45+/CD133+/CD73+ hematopoietic stem cells suggests a role for this channel in hematopoietic cell-derived tumors, i.e., leukemias and lymphomas.

Figure 1. TRPV2 regulation is involved in cancer-related cellular responses. (Siveen K S, et al., 2020.)

TRPV2 as a Drug Discovery Target

TRPV2 has three characteristics that make it an excellent therapeutic target. Firstly, TRPV2 is not present in the plasma membrane under normal conditions but translocates to the plasma membrane during disease states, where it contributes to excessive Ca²⁺ influx into the cells. Thus, a drug targeting TRPV2 would be selective for dysfunctional cells, not for normal cells. Secondly, there are two basic strategies to block TRPV2 signaling: Blocking TRPV2 accumulation in the plasma membrane (stimulating internalization) or Ca²⁺ influx. Thirdly, as [Ca²⁺]i overload by TRPV2 activation is a common factor in the terminal phase of muscular degenerative diseases, TRPV2 inhibition may be effective in the treatment of other dystrophinopathy-related diseases, although their responsible gene mutations have not been identified yet.

TRPV2 Gene Editing Services

CRISPR/Cas9 Platform^CB at Creative Biogene is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products for academic research, biotech research and pharmaceutical drug discovery. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we help you effectively control TRPV2 genes knockout/knockin/point mutation in cells or animals via CRISPR/Cas9 technology.

Service	Details	Alternative cell lines or animal species
TRPV2 Gene Editing Cell Line Generation	gRNA design and synthesis Transfect the cell lines you're interested Select the high expression cells and sort monoclonal cell Validate the knockout/knockin/point mutation of TRPV2 by PCR and sequencing Provide cryogenically preserved vials of stable cells and final reports	HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.
TRPV2 Gene Editing Animal Model Generation	TRPV2 gene conventional knockout animals TRPV2 gene conditional knockout animals TRPV2 point mutation animals TRPV2 knockin animals	Mouse, rat, rabbit, zebrafish, C. elegans, etc.

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