Research progress of TRPV4 in ocular pathophysiological function / 国际眼科杂志(Guoji Yanke Zazhi)

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.

Preliminary study of TRPV4 affects chondrocyte degeneration / 中国骨伤

OBJECTIVE@#To explore and verify that transient receptor potential vanilloid 4(TRPV4) affects chondrocyte degeneration.@*METHODS@#Neonatal SD rats were selected, primary chondrocytes were extracted, and identified by toluidine blue staining and alcian blue staining;an in vitro chondrocyte inflammation model was constructed by IL-1β, and TRPV4 inhibitor was used to treat chondrocytes under inflammatory conditions, and the chondrocytes were treated by RT-PCR method was used to detect matrix metallopeptidase 13(MMP-13), a disintegrin and metalloproteinase with thrombospondin 5, (ADAMTS-5)、nitric oxide synthase 2(NOS2)、Collagen, type II alpha 1(Col2α1)and aggrecan (Acan) mRNA in chondrocytes; primary chondrocytes were treated with different concentrations of TRPV4 overexpression plasmid, and the optimal overexpression dose was screened. The mRNA expressions of TRPV4, MMP-13, ADAMTS-5, NOS2, Col2α1 and Acan in chondrocytes under the optimal TRPV4 overexpression dose were detected.@*RESULTS@#Toluidine blue staining and Alcian blue staining identified the extracted cells as primary chondrocytes;RT-PCR showed that TRPV4, MMP-13, ADAMTS-5, NOS2 mRNA in chondrocytes treated with TRPV4 inhibitor under inflammatory conditions. The expression of Col2α1 mRNA was significantly decreased (P<0.05), and the expression of Col2α1 mRNA was increased (P<0.05). Although there was no significant difference in the expression of Acan mRNA, the overall trend was also increasing. The expression of Col2α1 and Acan mRNA in chondrocytes was significantly decreased (P<0.05), and the expression of NOS2 mRNA was increased(P<0.05), but there was no significant difference in MMP-13 and ADAMTS-5 (P>0.05).@*CONCLUSION@#Inhibiting the expression of TRPV4 can down-regulate the expression of genes related to chondrocyte degeneration.

Research progress of chondrocyte mechanotransduction mediated by TRPV4 and PIEZOs / 生物医学工程学杂志

Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Research progress of TRPV4 in glaucoma optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucomatous optic neuropathy(GON)is the difficulty of glaucoma treatment. In recent years, a variety of theories have been put forward about the pathogenesis of GON, but none of them can explain the principle of optic neuropathy caused by all types of glaucoma, which makes the disease difficult to treat in clinical treatment and is not conducive to early intervention. The latest research found that the transient receptor potential channel vanillic acid subfamily 4(TRPV4)in the retina plays an important role in various pathogenesis of GON. This article will review TRPV4 and its role in the occurrence and development of GON in order to find a common “connection point” for the multiple mechanism theories of GON, which will contribute to further understanding and clinical treatment of the disease.

Effect of TRPV4-Nox2 complex on aortic vasodilatory function of obese mice / 中国药理学通报

Aim To investigate the effects of TRPV4-Nox2 complex on ROS production and aortic vasodilatory function in mice fed with high-fat diet.Methods Male C57 BL/6J mice and TRPV4 KO mice were randomly divided into seven groups, with 10 mice in each group: normal diet group(ND), high-fat diet group(HFD), TRPV4 KO mice fed with high-fat diet group(TRPV4 KO-HFD), HFD+AAV-Flt1-Vector/Nox2 ▵3 group, TRPV4 KO-HFD+AAV-Flt1 -Vector/Nox2 ▵3 group.Body weight and blood pressure were recorded.14 weeks later primary aortic endothelial cells were isolated for CM-H2DCFDA staining and immuno-FRET assay, and aortic rings were isolated for vascular tone assay.Results ① Obesity significantly increased ROS production, triggered vasodilatory dysfunction and increased the strength of physical coupling between TRPV4-Nox2 complex(P<0.05); ② Decreasing the physical association of TRPV4-Nox2 complex could help reduce obesity-induced increased ROS production and vasodilatory dysfunction(P<0.05); ③ Entrectinib had no effect on the expression and function of TRPV4 and Nox2, but only decreased the physical association of the TRPV4-Nox2, which in turn improved obesity-induced oxidative stress and restored vasodilatory function.Conclusions Reducing the physical association of TRPV4 and Nox2 through Entrectinib can help reduce obesity-induced increase in ROS production and improve vasodilatory function of obese mice.

Baicalin treats cerebral ischemia reperfusion-induced brain edema in rats by inhibiting TRPV4 and AQP4 of astrocytes / 中国中药杂志

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.

Novel TRPV4 Pathogenic Variant in Severe Metatropic Skeletal Dysplasia: A Case Report

@#We report an eight-year-old girl with a novel homozygous TRPV4 gene pathogenic variant c.2355G>T p. (Trp785Cys) with mesomelic shortening, odontoid hypoplasia, multiple joint contractures, thoracolumbar kyphosis, pectus carinatum, halberd pelvis, and dumb-bell shaped long bones. The novel variant caused a severe recessive form of metatropic dysplasia.

TRPV4 induces apoptosis via p38 MAPK in human lung cancer cells

Lung cancer is one of the most common cancers worldwide. TRPV4 belongs to the 'transient receptor potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation, and inflammation. Unlike other TRP superfamily channels, its roles in cancers are unknown. Here, we elucidated the effects of TRPV4 and molecular mechanisms in human lung cancer cells. The levels of TRPV4 were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay. Cell apoptosis was determined by FACS assay. The results demonstrated that low levels of TRPV4 were detected in clinical lung carcinoma specimens. Over-expression of TRPV4 induced cell death and inhibited cell proliferation and migration in A549 cells and H460 cells. Moreover, over-expression of TRPV4 enhanced the activation of p38 MAPK signal pathway. Inhibition of p38 MAPK abolished the effects of TRPV4 on cell proliferation, apoptosis, and migration in A549 cells. Collectively, our findings indicated that TRPV4 induced apoptosis via p38 MAPK in human lung cancer cells and suggested that TRPV4 was a potential target for therapy of human lung cancers.

Implications of Transient Receptor Potential Cation Channels in Migraine Pathophysiology / 神经科学通报·英文版

Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive, abnormal trigeminal and central nervous system activity is likely to play an important role. Transient receptor potential (TRP) channels, which transduce noxious stimuli into pain signals, are expressed in trigeminal ganglion neurons and brain regions closely associated with the pathophysiology of migraine. In the trigeminal ganglion, TRP channels co-localize with calcitonin gene-related peptide, a neuropeptide crucially implicated in migraine pathophysiology. Many preclinical and clinical data support the roles of TRP channels in migraine. In particular, activation of TRP cation channel V1 has been shown to regulate calcitonin gene-related peptide release from trigeminal nerves. Intriguingly, several effective anti-migraine therapies, including botulinum neurotoxin type A, affect the functions of TRP cation channels. Here, we discuss currently available data regarding the roles of major TRP cation channels in the pathophysiology of migraine and the therapeutic applicability thereof.

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome / 神经科学通报·英文版

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.

Exploration on effect mechanism of Miao medicinal acupuncture therapy in treatment of knee osteoarthritis based on TRPV ion channel / 中国针灸

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.

Role and mechanism of TRP ion channels in pruritus / 中国药理学通报

Pruritus is an unpleasant noxious sensation induced by a variety of causes. Although pruritus does not cause death directly, long-term chronic pruritus severely reduces the quality of life of patients. TRP (transient receptor potential ion channels) participate in the physiological process from the sensation to skin balance. A large number of studies have confirmed that many itch media are involved in signal transduction related to TRP ion channels. We review the difference between itch and pain, and the role and mechanism of TRP in itch, so as to provide new research targets for treatment of pruritus.

High salt inhibits nitric oxide production in thoracic aortic endothelial cells and its mechanism / 中国药理学通报

Aim To investigate the effect of high-salt model of mouse thoracic aortic endothelial cells on the production of nitric oxide (NO) . Methods After preincubation of thoracic aortic endothelial cells with transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047, the effects of TRPV4 on NO production were studied by Ca2+and NO staining with calcium ion fluorescent probe Fluo-4 and NO fluorescent probe DAF-FM DA. The thoracic aortic endothelial cells were stimulated with a high salt concentration of 60 mmo! L"1 to detect Ca2+influx and NO production Compared with control group, suppression of TRPV4 inhibited Ca2+influx and NO production in thoracic aortic endothelial cells, and high salt conditions inhibited TRPV4-medicated Ca2+influx and NO production compared with mannitol under the same osmotic pressure. Conclusion In high salt state, the inhibition of TRPV4 channel leads to the decrease of Ca2+influx and the down-regulation of NO synthesis.

Decreased Expression of TRPV4 Channels in HEI-OC1 Cells Induced by High Glucose Is Associated with Hearing Impairment

PURPOSE: Previous reports have shown that hyperglycemia-induced inhibition of transient receptor potential vanilloid sub type 4 (TRPV4), a transient receptor potential ion channel, affects the severity of hearing impairment (HI). In this study, we explored the role of TRPV4 in HI using HEI-OC1 cells exposed to high glucose (HG). MATERIALS AND METHODS: HEI-OC1 cells were cultured in a HG environment (25 mM D-glucose) for 48 hours, and qRT-PCR and Western blotting were used to analyze the expression of TRPV4 at the mRNA and protein level. TRPV4 agonist (GSK1016790A) or antagonist (HC-067047) in cultured HEI-OC1 cells was used to obtain abnormal TRPV4 expression. Functional TRPV4 activity was assessed in cultured HEI-OC1 cells using the MTT assay and a cell death detection ELISA. RESULTS: TRPV4 agonists exerted protective effects against HG-induced HI, as evidenced by increased MTT levels and inhibition of apoptosis in HEI-OC1 cells. TRPV4 overexpression significantly increased protein levels of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), while TRPV4 antagonists had the opposite effect. Our results indicated that TRPV4 is a hyperglycemia-related factor that can inhibit cell proliferation and promote cell apoptosis by activating the MAPK signaling pathway in HEI-OC1 cells. CONCLUSION: Our results show that the overexpression of TRPV4 can attenuate cell death in HEI-OC1 cells exposed to HG.

Effect of TRPV4 on angiotensin II-induced renal injury in mice / 中国比较医学杂志

Objective This study was designed to determine the effect of transient receptor potential vanilloid type 4(TRPV4)on angiotensin Ⅱ(Ang Ⅱ)-induced renal injury in TRPV4-null mutant(TRPV4 -/-)mice. Methods The mice were divided into sham group and Ang Ⅱ-treated group. Ang Ⅱ was infused systemically into wild type(WT)and TRPV4 -/- mice via a miniosmotic pump for 4 weeks, and the sham mice were given with normal saline. Systolic blood pressure,urinary excretion of albumin and 8-isoprostane, serum creatinine, and the pathological changes in the kidney tissues were assayed after the 4-week treatment. Results Compared with corresponding sham mice,Ang Ⅱ infusion led to enhanced systolic blood pressure,increased urinary excretion of albumin and 8-isoprostane,increased serum creatinine(P< 0.05),and enhanced glomerulosclerosis degree and renal tubulointerstitial injury index(P< 0.05)in the WT and TRPV4 -/- mice. The result were associated with enhanced collagen levels in the kidney(P< 0.05). All of them were attenuated by the deletion of TRPV4 in the absence of alteration in blood pressure(P< 0.05). Conclusions Deletion of TRPV4 could alleviate renal injury during Ang Ⅱ-induced hypertension, suggesting that TRPV4 may contribute to the pathophysiology of angiotensin Ⅱ-induced renal injury.

Effects of total flavones of rhododendra on transient receptorpotential vanilloid receptor 4 in cerebral basilar arteries ofrats subjected to ischemia/reperfusion injury / 中国药理学通报

Aim To research the effects of total flavones of rhododendra(TFR)on transient receptor potential vanilloid receptor 4(TRPV4)in cerebral basilar arteries(CBA)of rats subjected to ischemia/reperfusion(IR)injury.Methods The model of total brain IR was established by four-artery occlusion(4-VO)method in rats.Arterial pressure perfusion and cell membrane potential recording methods were used for surveying the dilatation and hyperpolarization of TFR and ruthenium red(RR,an inhibitor of TRPV4)in the KCl-preconstricted CBA ex vivo in rats subjected to IR.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were utilized to investigate the TRPV4 mRNA and protein expressions of TFR and RR in cerebrovascular endothelial cells of CBA in vivo in rats subjected to IR.Results 11～2 700 mg·L-1 TFR significantly induced concentration-dependent hyperpolarization and dilatation in the KCl-preconstricted CBA in rats subjected to IR.TFR still produced degenerative hyperpolarization and dilatation by removal of endothelium in CBA,which was remarkably attenuated as compared with endothelium-intact group(P<0.01).After removal of NO and PGI2 vasodilatation,TFR obviously elicited the hyperpolarization and dilatation that were further decreased by RR(an inhibitor of TRPV4)in IR CBAs.TFR pretreatment apparently increased the level of TRPV4 mRNA and protein expressions in IR CBAs.These effects were restrained by RR,an inhibitor of TRPV4.Conclusions TFR could mediate endothelium-dependent and endothelium-independent effects.The endothelium-derived dilatation may be related to the increase of endothelium activity and endothelium-derived hyperpolarizing factor(EDHF)generation and release that have been promoted by TFR,and secondarily activating TRPV4,which results in Ca2+ inflow and subsequent hyperpolarization of vascular smooth muscle cell membrane and vasorelaxation.

Metatropic Dysplasia with a Novel Mutation in TRPV4.

Back ground: Metatropic dysplasia is a skeletal dysplasia characterized by rhizomelia, severe kyphoscoliosis and a coccygeal tail. Case characteristics: A 12 day-old male neonate had facial dysmorphism, short limbs and coccygeal tail and showed radiological features of metatropic dysplasia. Observation: A novel heterozygous variant was observed in TRPV4 gene. Message: We report a novel mutation in an Indian neonate with metatropic dysplasia.

High salt diet enhances the physical coupling between TRPV4 and cPLA2 / 中国药理学通报

Aim To observe the physical coupling between transient receptor potential channel vanilloid type 4 (TRPV4 ) and cPLA2 in endothelial cells. Methods We investigated the physical association of TRPV4-cPLA2 coupling by immunofluorescence reso-nance energy transfer (immuno-FRET)to assess the spatial proximity between TRPV4 and cPLA2 in human microvascular endothelial cells (HMEC),primary cul-tured endothelial cells and in thoracic aortas rings from high salt-induced hypertension mice.Results At the cellular level,with high salt treatment,the physical in-teraction of TRPV4 and cPLA2 was significantly en-hanced in primary vascular endothelial cells and HMEC.Furthermore, in thoracic aortas rings from high salt-induced hypertension mice,we found an in-creases interaction between TRPV4 and cPLA2 in en-dothelial cells from arterial segments .Conclusion High-salt treatment increases the endothelial TRPV4-cPLA2 coupling,indicating that this coupling may pro-vide a new target for vascular endothelial dysfunction.

Displasia metatrópica en una niña con mutación c. 1811_1812delinsAT en el exón 11 del gen TRPV4 no informada previamente / Metatropic dysplasia in a girl with c. 1811_1812delinsAT mutation in exon 11 of the TRPV4 gene not previously reported

La displasia metatrópica es una alteración esquelética con heterogeneidad clínica, caracterizada por dismorfias craneofaciales, que incluyen prominencia frontal e hipoplasia medio facial, tronco corto con cifoescoliosis progresiva y acortamiento de las extremidades. El gen TRPV4 se localiza en 12q24.11; codifica a un canal de catión con permeabilidad no selectiva al calcio, el cual se expresa y participa en muchos procesos fisiológicos en respuesta a diversos estímulos. Más de 50 mutaciones en TRPV4 han sido descritas. Se presenta el caso de una niña de 7 meses de edad con mutación heterocigota c.1811_1812delinsAT; p.I604N en el intrón 11 no informada previamente en el gen TRPV4 y con hallazgos clínicos compatibles con displasia metatrópica.

Metatropic dysplasia is a skeletal disorder with clinical heterogeneity, characterized by craniofacial dysmorphy including frontal bossing and midface hypoplasia, short trunk, progressive kyphoscoliosis and shortened limbs. The TRPV4 gene is located on 12q24.11, coding a cation channel with non-selective permeability to calcium; it is expressed and involved in many physiological processes through responses to different stimuli. Over 50 mutations in TRPV4 have been described. We present a seven months old girl with heterozygous mutation c.1811_1812delinsAT; p.I604N in intron 11 not previously reported in the TRPV4 gene and with clinical findings compatible with metatropic dysplasia