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Transient receptor potential vanilloid receptor 4(TRPV4)is a non-selective cation channel responsible for sensing changes in cell swelling, temperature, mechanical stretch, shear stress and osmotic pressure by regulating transmembrane calcium signaling and thereby influencing gene expression, cell morphology, and cytoskeletal construction. TRPV4 is widely expressed throughout the body. Intraocularly, TRPV4 is functionally expressed in the cornea, lens, ciliary body, trabecular meshwork and retina. In this article, the expression and physiopathological functions of TRPV4 in various tissues of the eye were described. With the in-depth study of TRPV4 in ocular pathophysiological functions, TRPV4 may become a potential drug target in corneal injury repair, glaucoma and retinal angiogenesis, but further in-depth study is still needed.
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As a member of the transient receptor potential ion channel family, transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel and is widely distributed in a variety of tissues and organs. In recent years, more and more studies have shown that TRPV4 channel proteins are closely associated with liver diseases such as liver fibrosis, liver cancer, and polycystic liver disease. This article analyzes the articles on TRPV4 and liver disease and summarizes the exact signaling pathways and possible potential mechanism between TRPV4 and liver disease, so as to provide new ideas for clinical application and further studies.
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Objective To construct a high-throughput screening model for transient receptor potential vanilloid 4 (TRPV4) channel modulators based on calcium-activated chloride channels (CaCC). Methods RT-PCR was used to detect the endogenous expression of TRPV4 in Fischer rat thyroid (FRT) cells. The PCR products obtained were subjected to nucleic acid sequencing using gel-recovery technology. Western blotting was employed to detect the expression of TRPV4 protein in FRT cells. The liposome transfection method was applied to construct the FRT cell model that co-expressed anoctamin 1 (ANO1) and YFP-H148Q/ I152L. The expressions of ANO1 and YFP-H148Q/I152L in cells were identified by the inverted fluorescence microscope and the fluorescence quenching kinetics test. After adding TRPV4 activators and inhibitors, the fluorescence quenching kinetics experiment was used to test whether the model could screen TRPV4 modulators. The Fura-2 fluorescent probe method was applied to detect the calcium concentration in cells after adding TRPV4 activators; The Z' factor was calculated to evaluate the sensitivity and specificity of the cell model. Results RT-PCR and Western blotting confirmed the endogenous expression of TRPV4 in FRT cells; ANO1 was clearly expressed on the FRT cell membrane and YFP-H148Q/I152L was clearly expressed in the cytoplasm of FRT cells under the inverted fluorescence microscope. The FRT cell model co-expressing ANO1 and YFP-H148Q/I152L was successfully constructed. Fluorescence quenching kinetics experiments confirmed that the model could screen TRPV4 regulators, and the slope value of fluorescence change and the concentration of TRPV4 regulator concentration were in a dose-dependent manner. The model could sensitively detect changes in intracellular calcium concentration, and the slope value could reflect intracellular calcium concentration. The Z' factor was 0.728, which demonstrates its capacity for high-throughput screening. Conclusions We successfully constructed a high-throughput model that could screen TRPV4 modulators sensitively and efficiently.
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OBJECTIVE@#To observe the effect of Miao medicinal acupuncture therapy on transient receptor potential vanilloid (TRPV) channel in knee joint synovial tissue of the rabbits with knee osteoarthritis (KOA) model and to explore the mechanism of Miao medicinal acupuncture therapy in treatment of KOA.@*METHODS@#Of 34 New Zealand male rabbits, 6 rabbits were selected randomly as the normal group. KOA model was established in the rest rabbits by injecting a mixture of papain and L-cysteine in right knee joints. The 24 successfully modeled rabbits were randomized into a model group, a Miao medicinal acupuncture therapy group, a dermal needle group and a smearing group, 6 rabbits in each one. In the Miao medicinal acupuncture therapy group, Miao medicinal acupuncture therapy was adopted, in which, the roller type of dermal needle was used on the surface of right knee joint [a rectangle shape formed by "Xuehai" (SP 10), "Liangqiu" (ST 34), "Yanglingquan" (GB 34) and "Yinlingquan" (SP 9)], rolling in a " shape, on which, Miao medicinal solution was smeared in advance. In the dermal needle group, the rolling stimulation was exerted on the right the right knee joint surface with the roller type of dermal needle. In the smearing group, Miao medicinal solution was smeared on the right knee joint surface. The intervention was given once every two days, 3 times weekly and the intervention was exerted consecutively for 4 weeks. Successively, on day 1, 21, 28, 35, 42 and 49 of experiment, paw withdrawal threshold (von Frey threshold) after mechanical stimulation was detected in the rabbits. HE staining was adopted to observe the histomorphological changes of the right knee joint cartilage in the rabbits. ELISA was used to determine the contents of interleukin-1 (IL-1β) and tumor necrosis factor-α (TNF-α) in the right knee synovial fluid. Western blot method and real-time PCR were used to determine the relative expressions of protein and mRNA of TRPV1 and TRPV4 in knee synovial tissue of the rabbits.@*RESULTS@#Compared with the normal group, on day 49 of experiment, von Frey threshold was reduced significantly in the rabbits of the model group (@*CONCLUSION@#Miao medicinal acupuncture therapy plays a role in treatment of KOA probably through inhibiting the expressions of IL-1β and TNF-α of knee synovial fluid and down-regulating the expressions of protein and mRNA of TRPV1 and TRPV4 in knee synovial tissue.
Subject(s)
Animals , Male , Rabbits , Acupuncture Therapy , Knee Joint , Osteoarthritis, Knee/therapy , Synovial Fluid , Transient Receptor Potential ChannelsABSTRACT
Objective:To observe the effect of Shaoyao Gancaotang and its disassembled prescriptions on the expressions of transient receptor potential vanilloid 3 (TRPV3) and transient receptor potential vanilloid 4 (TRPV4) in myocardium and hypothalamus of rats in the ultra-high temperature environment, in order to explore the mechanism of Shaoyao Gancaotang and its disassembled prescriptions against the high temperature. Method:Seventy five male SPF-grade SD rats were randomly divided into 5 groups according to their body weight, namely normal control group, high temperature normal control group, Shaoyao Gancaotang group (2.16 g·kg-1), single Paeoniae Radix Alba(PRA) group (1.08 g·kg-1) and single Glycyrrhizae Radix et Rhizoma(GRR) group (1.08 g·kg-1). Except normal control group, the remaining groups were fed in artificial climate boxes for 13 days. The normal control group and the high temperature normal control group were given the same volume of pure water. Western blot and quantitative real-time fluorescence polymerase chain reaction(Real-time PCR) were used to determine expressions of TRPV3, TRPV4 protein and mRNA in myocardium and hypothalamus of each group. Result:Compared with the normothermic control group, the expressions of TRPV3 protein, TRPV4 mRNA, TRPV3 protein and TRPV3 mRNA in the myocardium of the hyperthermic control group were significantly higher than those of the normal control group (PPPConclusion:TRPV3, TRPV4 channels in rat myocardium and hypothalamus were activated in the high temperature environment. The anti-hyperthermic mechanism of Shaoyao Gancaotang and its disassembled prescriptions was related to the regulation of TRPV3, TRPV4 channel protein and mRNA expressions in rat myocardium and hypothalamus.
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Aim: To verify the involvement of transient receptor potential vanilloid 4 (TRPV4) in the process of progesterone induced body temperature rise in female rats during their sexual cycle. Methods: The body temperature and progesterone concentration at different stages of the normal female rats' sexual cycle were measured. The ovariectomized rats were given different doses of progesterone and their body temperature were measured. Female rats were administered with RN-1734, a specific antagonist of TRPV4 in the preoptic-anterior hypothalamus area (PO/AH) at the metestrus to observe the change of rats body temperature. Furthermore, RN 1734 was injected into the PO/AH area of ovariectomized rats which were preinjected with progesterone. The effect of progesterone on the body temperature of rats and the fluctuation of body temperature after blocking TRPV4 were observed. Results: There was a positive correlation between body temperature and progesterone doses in female rats at different stages of estrus cycle. In ovariectomized rats, different doses of progesterone were administered, indicating a dose-dependent increase in body temperature. RN- 1734 was injected to PO/AH 2 hours before the maximum body temperature on normal metestrus rats. It was observed that the increase range of body temperature decreased significantly after RN-1734 injection. This study also showed that RN-1734 significantly reduced the increase range of body temperature in ovariectomized rats administered with progesterone. Conclusions: The specific antagonist TRPV4 injected into the thermoregulation center could reduce the increase of body temperature in metestrus of normal rats, suggesting that TRPV4 may be involved in the process of the increase of rat body temperature induced by progesterone.
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Objective To summarize the clinical,radiographic and genetic features of a family with metatropic dysplasia,in order to improve the level of understanding and diagnosis of this disease.Methods The proband,a one-year old boy,was diagnosed as metatropic dysplasia.His mother was 26 years old with mildly phenotype.Their clinical features and bone X-ray findings were analyzed.The DNA samples of the proband and his parents were collected.The coding exons and flanking introns regions of transient receptor potential vanilloid 4 (TRPV4) gene were amplified by polymerase chain reaction (PCR) and analyzed by DNA automatic detector.The pathology,diagnosis,treatment and prognosis were expounded.Results The symptoms of the boy were characterized by short extremities,a short trunk with progressive kyphoscoliosis,and craniofacial abnormalities that include a prominent forehead,midface hypoplasia,and a squared-off jaw.His motor development was slightly delayed.Mental development was normal.Bone X ray of the boy showed platyspondyly and severe metaphyseal enlargement with shortening of long bones and irregularities and delayed ossification of epiphysis.The patient and his mother were heterozygous for the nucleotide substitutions c.2396 ＞ T (p.P799L) in TRPV4 gene.Conclusions The patient and his mother with metatropic dysplasia were diagnosed with TRPV4 gene analysis.The patient showed typical clinical features.His mother was mild.Metatropic dysplasia had significantly clinical heterogeneity.Gene analysis is helpful for the diagnosis.
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To analyze recent studies on the role of transient receptor potential vanilloid 4 (TRPV4) in fibrosis diseases and related mechanism. TRPV4 is a class of non-selective cation channel protein, which involved in intracellular divalent cations, mainly regulate Ca2+ homestasis and participate in the development of multiple organ fibrosis broadly. TRPV4 plays an important role in the prevention and treatment of fibrosis diseases. But for its complex mechanism of action, further research needs to be studied.