TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6)

No difference was observed in the number of goblet cells between WT and TRPV6KO mice; however, the expression of intercellular junction proteins, including E-cadherin, claudin-3, and occludin, was significantly suppressed in TRPV6KO mice compared with WT mice. These findings suggest that TRPV6 protects against DSS-induced colitis, potentially by regulating epithelial barrier function through intracellular junction protein expressions.

Our results establish TRPV6 as a functional target of lidocaine and provide a mechanistic basis for repurposing this anesthetic as an ablation sensitizer in CCA. This strategy offers a clinically applicable approach to overcome tumor thermotolerance and enhance the efficacy of thermal ablation in cholangiocarcinoma.

Functional studies reveal that HOMER3 overexpression enhances ECM stiffness, type I collagen deposition, and Aβ accumulation in the tumor stroma, leading to tumor growth and aggressiveness, while HOMER3 knockdown reduces ECM stiffness, disrupts collagen composition, and increases sensitivity to docetaxel. These findings establish HOMER3 as a pivotal regulator of OSCC malignancy and chemoresistance, providing novel insights into its role in orchestrating the tumor microenvironment and identifying it as a promising therapeutic target for OSCC.

Functionally impaired TRPV6 variants significantly influenced the clinical outcomes of chronic pancreatitis. TRPV6 in pancreatic acinar cells might play a protective role against pancreatitis in mice.

When bound to the D489-D580 site, Mg2+ prevents the α-to-π transition in the middle of S6 that accompanies channel opening, thus maintaining S6 entirely α-helical, locking the channel in the closed state and inhibiting TRPV6-mediated currents. Further exploration of this inhibitory mechanism may help to develop future strategies for the treatment of TRPV6-associated diseases.

Treatment with verapamil, an L-type Ca2+ channel inhibitor, significantly reduced Cd uptake in UMR-106 cells...However, the degree of reduction ranged from 15 to 35%, indicating that no single pathway makes a predominant contribution. These findings suggest that diverse pathways, encompassing metal transporters and Ca2+ channels, contribute to Cd uptake in UMR-106 cells, although no single pathway predominates.

When AMD3100, a selective inhibitor of the CXCR4 receptor, was combined with AMD3100, a synergistic effect on the suppression of metastasis development was achieved. Thus, the suppression of CRPC metastasis to bone can be achieved via simultaneous targeting of TRPV6/CXCR4, demonstrating that combined therapy is a proof-of-concept approach in vivo.

Key recommendations encompass the following aspects: Supplementing statistical power justification through explicit definition of parameters including ≥80% desired power, minimal effect size, and intra-group variability; Report exact P values with confidence intervals to improve statistical transparency; Clarification of p38 MAPK versus cPLA2 pathway contributions via co-inhibition experiments; Exclusion of TRP channel confounding effects when using 2-APB through targeted TRPV6 inhibition; Distinction between direct Cd²⁺ effects and toxicity-induced compensatory responses; Provision of explicit rationale for selecting Mag-Fluo-4/AM and Rhod-2/AM fluorescent probes; Experimental verification of PMCA inhibition synergism with cadmium-induced cytosolic Ca²⁺ overload. These recommendations would enhance the robustness of the original study's conclusions.

Further analysis of somatic mutations suggests that the specific inner LWI regions of TRPV5 (first 3) and TRPV6 (first 5) impose mutational hot-spots that are linked with different cancers. These findings may have broad significance in designing pharmacological agents for targeting TRPV5 and TRPV6 separately or simultaneously.

However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe-TRPV6 + si-PKA group. In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway.

In this review, we will dissect the contribution of TRP channels in such hallmarks of PCa and then discuss their applicability as new prognostic and therapeutic agents in the fight against metastatic PCa. In particular, the great potential of TRPM8, TRPV6, and TRPA1 in opening the way to new treatment perspectives will be highlighted.

Functional properties assessed by electrophysiological recordings and Ca2+ uptake measurements, and water and ion permeation evaluated by molecular modeling also appear similar between the haplotypes. Therefore, ancestral and derived TRPV6 have similar structure and function, implying that other factors are responsible for the differences in susceptibility to cancer.