TRP

Trp
  • 文章类型: Journal Article
    背景:瞬时受体电位(TRP)通道参与肿瘤的发展和进展。然而,它们在结直肠癌(CRC)中的作用尚不清楚,本研究旨在探讨TRP相关基因在CRC中的作用。
    方法:数据来自癌症基因组图谱(TCGA)数据库,并对GSE14333和GSE38832数据集进行了分析,以评估预后和标记TRP相关基因(TRGs)。随后,进行聚类分析和免疫浸润分析以探索相关的TRGs。使用人结肠癌细胞进行关键TRGs基因和蛋白质表达的体外验证。
    结果:与正常组织相比,8个TRGs在CRC中显著上调,而11人被下调。TRPA1被确定为保护性预后因素,而TRPM5(HR=1.349),TRPV4(HR=1.289),和TRPV3(HR=1.442)被确定为预后危险因素。接收器工作特征(ROC)曲线和Kaplan-Meier(KM)分析产生了类似的结果。此外,TRPA1的低表达和TRPV4、TRPM5的高表达与患者预后呈负相关,和实验验证证实了TRPA1的低表达和TRPV4和TRPM5在CRC细胞系中的过表达。
    结论:本研究确定了CRC中TRP通道相关的预后,提供了一种新的方法来分层CRC预后。
    BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC.
    METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs\' gene and protein expression was conducted using human colon cancer cells.
    RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines.
    CONCLUSIONS: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.
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  • 文章类型: Journal Article
    这项研究的目的是调查光疗对生物蝶呤(BH4)的整体影响,新蝶呤(BH2),色氨酸(Trp),卒中后抑郁患者的行为神经炎症反应。从2021年2月至2022年12月,我院共有100名中风后抑郁症住院患者。参与者被随机分配到对照组或实验组。对照组给予常规治疗,包括药物治疗和心理支持,实验组每天接受30分钟的光疗,共8周。所有参与者自愿参与研究并提供知情同意书。对患者的基线特征进行统计学分析。使用汉密尔顿抑郁量表(HAMD)和贝克抑郁量表(BDI)评估抑郁症状的严重程度。氨基酸神经递质的水平,包括γ-氨基丁酸(GABA),天冬氨酸(Asp),和谷氨酸(Glu),使用放射免疫分析法进行测量。血浆神经炎因子水平,如TNF-α,IL-6和IL-1β分别为,使用ELISA测定。通过HPLC检测BH4、BH2和Trp的血浆水平。SOD的水平,GPx,CAT,使用相应的试剂盒和比色法测量血浆中的MDA和MDA。使用SF-36量表评估生活质量。两组患者基线特征差异无统计学意义(P>0.05)。试验组HAMD、BDI评分低于对照组(P<0.05),提示光疗可以降低卒中后抑郁的严重程度.GABA的水平,Glu,与治疗前比较,两组治疗后Asp和Asp均明显升高(P<0.01)。实验组GABA水平高于对照组(P<0.01),而Glu的水平,Asp低于对照组(P<0.01)。血浆TNF-α水平,实验组IL-6、IL-1β水平明显低于对照组(P<0.05)。此外,实验组BH4、Trp水平明显高于对照组(P<0.05),而实验组BH2水平明显低于对照组(P<0.05)。此外,SOD的水平,GPx,实验组CAT明显高于对照组(P<0.05),实验组MDA水平显著低于对照组(P<0.05)。实验组在身体机能方面得分较高,心理健康,社会功能,总体健康状况与对照组比较(P<0.05)。光疗对BH4,BH2和Trp的代谢产生了深远的影响,以及中风后抑郁症患者的行为神经炎症反应和生活质量。通过其优化神经递质分泌和合成的能力,光疗有效调节神经炎症反应,改善生化参数,增强抗氧化能力,缓解抑郁症状.因此,光疗被认为是卒中后抑郁患者的一种有价值的辅助治疗方法.
    The aim of this study was to investigate the overall effects of phototherapy on biopterin (BH4), neopterin (BH2), tryptophan (Trp), and behavioral neuroinflammatory reaction in patients with post-stroke depression. There involved a total of 100 hospitalized patients with post-stroke depression at our hospital from February 2021 to December 2022. The participants enrolled were randomly assigned to either the control group or the experimental group. The control group received routine treatment, including medication and psychological support, while the experimental group received 30 min of phototherapy daily for 8 weeks. All participantsvoluntarily participated in the study and provided informed consent. Baseline characteristics of the patients were statistically analyzed. The severity of depressive symptoms was evaluated using the hamilton depression scale (HAMD) and the beck depression inventory (BDI). Levels of amino acid neurotransmitters, including gamma-aminobutyric acid (GABA), aspartic acid (Asp), and glutamic acid (Glu), were measured using radioimmunoassay. Plasma levels of neuroinflammatory factors, such as TNF-α, IL-6, and IL-1β were, determined using ELISA. Plasma levels of BH4, BH2, and Trp were detected by HPLC. Levels of SOD, GPx, CAT, and MDA in plasma were measured using corresponding kits and colorimetry. Quality of life was assessed using the SF-36 scale. There were no differences in baseline characteristic between the two groups (P > 0.05). The HAMD and BDI scores in the experimental group were lower than those in the control group (P < 0.05), indicating phototherapy could reduce the severity of post-stroke depression. The levels of GABA, Glu, and Asp in both groups significantly increased after treatment compared to their respective levels before treatment (P < 0.01).The levels of GABA in the experimental group were higher than those in the control group (P < 0.01),while the levels of Glu, and Asp were lower than those in the control group (P < 0.01). The plasma levels of TNF-α, IL-6, and IL-1β in the experimental group were evidently lower than those in the control group (P < 0.05). Moreover, the levels of BH4 and Trp in experimental group were significantly higher than those in the control group (P < 0.05), while the levelsof BH2 in the experimental group were significantly lower than the control group (P < 0.05). Additionally, the levels of SOD, GPx, and CAT in the experimental group were evidently higher than those in the control group (P < 0.05), whereas the levels of MDA in the experimental group were significantly lower than control group (P < 0.05). The experimental group showed higher scores in physical function, mental health, social function, and overall health compared to the control group (P < 0.05). Phototherapy exerted a profound impact on the metabolism of BH4, BH2, and Trp, as well as on behavioral neuroinflammatory reactions and the quality of life in patients suffering from post-stroke depression. Through its ability to optimize the secretion and synthesis of neurotransmitters, phototherapy effectively regulated neuroinflammatory reactions, improved biochemical parameters, enhancedantioxidant capacity, and alleviated depressive symptoms. As a result, phototherapy was considered a valuable adjuvant therapeutic approach for patients with post-stroke depression.
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  • 文章类型: Journal Article
    瞬时受体电位通道规范5(TRPC5)是非选择性离子通道;通过TRPC5的离子流入导致下游信号通路的激活。此外,TRPC5已被确定为在病理过程中具有潜在的作用,特别是在由细胞阳离子稳态失调引起的疾病中,如支气管哮喘或肺动脉高压。然而,TRPC5在人肺中的表达和分布尚不清楚。迄今为止,TRPC5仅在人肺中的几种细胞类型中检测到,如气道,肺静脉和动脉平滑肌细胞。因此,本研究旨在研究TRPC5在人肺中的蛋白表达并评估其组织学分布。从六个保存的身体供体获得人肺样品。处理后,苏木精和伊红染色,以及免疫组织化学。显微镜分析显示所有检查的肺结构中的中强免疫染色信号,包括胸膜,肺动脉和静脉,细支气管,肺泡间隔,1型和2型肺细胞,以及肺泡巨噬细胞。目前的研究表明,TRPC5可能参与人类肺部的各种病理过程,并且已经确定了一些影响TRPC5功能的药理化合物。因此,TRPC5可能为多种肺部疾病的治疗干预提供新的药物靶点。本研究的结果表明TRPC5蛋白在人肺的所有检查的组织学结构中表达。这些发现表明,TRPC5对肺中的生理细胞功能和病理生理细胞功能障碍可能比目前已知的更为重要。需要进一步的研究来探索TRPC5在人肺中的作用和治疗靶标潜力。
    Transient receptor potential channel canonical 5 (TRPC5) is a non-selective ion channel; ion influx through TRPC5 causes activation of downstream signaling pathways. In addition, TRPC5 has been identified as having a potential role in pathological processes, particularly in diseases caused by cellular cation homeostasis dysregulation, such as bronchial asthma or pulmonary hypertension. However, the expression and distribution of TRPC5 in the human lung remain unclear. To date, TRPC5 has only been detected in a few cell types in the human lung, such as airway, pulmonary venous and arterial smooth muscle cells. The present study therefore aimed to investigate the protein expression of TRPC5 in the human lung and to evaluate its histological distribution. Human lung samples were obtained from six preserved body donors. After processing, both hematoxylin & eosin staining, as well as immunohistochemistry were performed. Microscopic analysis revealed medium to strong immunostaining signals in all lung structures examined, including the pleura, pulmonary arteries and veins, bronchioles, alveolar septa, type 1 and 2 pneumocytes, as well as alveolar macrophages. Current research suggests that TRPC5 may be involved in various pathological processes in the human lung and some pharmacological compounds have already been identified that affect the function of TRPC5. Therefore, TRPC5 may present a novel drug target for therapeutic intervention in various lung diseases. The results of the present study indicate that the TRPC5 protein is expressed in all examined histological structures of the human lung. These findings suggest that TRPC5 may be more important for physiological cell function and pathophysiological cell dysfunction in the lung than is currently known. Further research is needed to explore the role and therapeutic target potential of TRPC5 in the human lung.
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  • 文章类型: Journal Article
    咖啡因(1,3,7-三甲基黄嘌呤)是一种天然存在的甲基黄嘌呤,在60多种不同的植物和水果中作为一种有效的中枢神经系统兴奋剂。虽然含咖啡因的饮料被广泛而随意地消费,自记录开始使用以来,人们已经认识到将超出饮食水平的咖啡因用作药物治疗。咖啡因的镇痛和血管活性是众所周知的,但其分子基础的程度仍然是一个活跃的研究领域。文献中有关于咖啡因对TRP通道的影响的现有证据,咖啡因在疼痛管理和镇痛中的作用,以及TRP在疼痛和镇痛中的作用;然而,关于咖啡因和TRP通道之间的相互作用,目前尚待进行综述.尽管咖啡因对TRP的影响已在实验室和动物模型中得到证实,关于咖啡因作为TRP调节剂的临床效用,缺乏大规模收集的数据.这篇综述旨在通过验证咖啡因作为瞬时受体电位(TRP)通道的调节剂来促进进一步的分子研究,以阐明咖啡因与TRP之间的特异性配体-宿主相互作用-重点是瞬时受体电位香草酸1(TRPV1)受体和瞬时受体电位锚蛋白1(TRPA1)受体亚型-及其在疼痛领域的应用。
    Caffeine (1,3,7-trimethylxanthine) is a naturally occurring methylxanthine that acts as a potent central nervous system stimulant found in more than 60 different plants and fruits. Although caffeinated beverages are widely and casually consumed, the application of caffeine beyond dietary levels as pharmacologic therapy has been recognized since the beginning of its recorded use. The analgesic and vasoactive properties of caffeine are well known, but the extent of their molecular basis remains an area of active research. There is existing evidence in the literature as to caffeine\'s effect on TRP channels, the role of caffeine in pain management and analgesia, as well as the role of TRP in pain and analgesia; however, there has yet to be a review focused on the interaction between caffeine and TRP channels. Although the influence of caffeine on TRP has been demonstrated in the lab and in animal models, there is a scarcity of data collected on a large scale as to the clinical utility of caffeine as a regulator of TRP. This review aims to prompt further molecular research to elucidate the specific ligand-host interaction between caffeine and TRP by validating caffeine as a regulator of transient receptor potential (TRP) channels-focusing on the transient receptor potential vanilloid 1 (TRPV1) receptor and transient receptor potential ankyrin 1 (TRPA1) receptor subtypes-and its application in areas of pain.
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  • 文章类型: Journal Article
    [目的]比较粒子束疗法(PT)与光子放疗(RT)治疗颅底脊索瘤的疗效。[方法]对1990-2022年报道的PT或光子RT治疗颅底脊索瘤进行系统评价。提取总生存期(OS)和无进展生存期(PFS)的数据,晚期不良事件,年龄,性别,总切除率(GTR),肿瘤体积,总辐照剂量,和治疗方式。对每个结果进行随机效应荟萃回归分析,以治疗方式作为解释变量,以比较方式。[结果]对30篇文章进行的荟萃分析发现,PT的3年和5年OS率与光子RT或联合光子RT/质子束治疗(PBT)为90.8%(95%CI:87.4-93.3%)与89.5%(95%CI:83.0-93.6%),p=0.6543;80.0%(95%CI:75.7-83.6%)与89.5%(95%CI:83.0-93.6%),p=0.6787。PT的5年PFS率与光子RT或光子RT/PBT为67.8%(95%CI:56.5-76.7%)40.2%(95%CI:31.6-48.7%),p=0.0004。随机效应模型显示,治疗方式(PT与光子RT或光子RT/PBT)不是3年OS(p=0.42)和5年OS(p=0.11)的重要因素,但却是5年PFS的重要因素(p<0.0001)。PT后的脑坏死率为8-50%,光子RT或光子RT/PBT后的脑坏死率为0-4%。[结论]这项研究表明,与光子RT相比,PT导致颅底脊索瘤的PFS更高,但是PT脑坏死的发生率有较高的趋势。需要发表和分析进一步的研究来验证这些发现。
    [Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4-93.3%) vs. 89.5% (95% CI: 83.0-93.6%), p = 0.6543; 80.0% (95% CI: 75.7-83.6%) vs. 89.5% (95% CI: 83.0-93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5-76.7%) vs. 40.2% (95% CI: 31.6-48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8-50% after PT and 0-4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings.
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  • 文章类型: Journal Article
    眼内压和外压的改变与青光眼的发病机制密切相关,创伤性视网膜损伤(TRI),和其他视网膜疾病,近几十年来,据报道视网膜神经元表达多个机械敏感通道(MSCs)。然而,MSCs在视觉功能和压力相关视网膜疾病中的作用尚不清楚.本文将重点介绍对K+具有渗透性的MSCs的多样性和功能意义,Na+,和Ca2+,主要包括大钾通道(BK);双孔结构域钾通道TRAAK和TREK;Piezo;上皮钠通道(ENaC);以及视网膜光感受器中的瞬时受体电位通道香草酸TRPV1,TRPV2和TRPV4,双极细胞,水平单元格,无长突细胞,和神经节细胞.大多数MSC不直接介导脊椎动物视网膜中的视觉信号。另一方面,一些研究表明,MSCs在生理条件下可以开放,调节视网膜神经元的活动。虽然这些数据合理地预测了视觉和机械信号的交叉,视网膜光路如何处理内源性和外源性机械刺激是不确定的。
    Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+, Na+, and Ca2+, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and TRPV4 in retinal photoreceptors, bipolar cells, horizontal cells, amacrine cells, and ganglion cells. Most MSCs do not directly mediate visual signals in vertebrate retinas. On the other hand, some studies have shown that MSCs can open in physiological conditions and regulate the activities of retinal neurons. While these data reasonably predict the crossing of visual and mechanical signals, how retinal light pathways deal with endogenous and exogenous mechanical stimulation is uncertain.
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  • 文章类型: Journal Article
    自身免疫性疾病是由多种因素引起的机体病理性自身免疫反应,会导致组织损伤和器官功能障碍。它们可分为器官特异性和全身性自身免疫性疾病。这些疾病通常涉及各种身体系统,包括血,肌肉,骨头,关节和软组织。瞬时受体电位(TRP)和PIEZO受体,这导致大卫·朱利叶斯和阿德姆·帕塔波蒂安在2021年获得诺贝尔生理学或医学奖,引起了人们的关注。目前关于TRP和PIEZO受体在自身免疫性疾病中的研究大多是在动物模型上进行的,仅进行了很少的临床研究。因此,本研究旨在回顾TRP和PIEZO的现有研究,以了解这些受体在自身免疫性疾病中的作用,这可能有助于阐明新的治疗策略。
    Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people\'s attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.
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  • 文章类型: Systematic Review
    软骨肉瘤是一种罕见的恶性骨肿瘤。粒子束疗法(PT)可以将剂量集中到目标,同时减少不良事件。进行了基于文献综述的荟萃分析,以检查PT和光子放疗对颅底软骨肉瘤的疗效。
    使用1990年至2022年发表的21篇文章进行了荟萃分析。
    PT后,3年和5年总生存率(OS)分别为94.1%(95%置信区间[CI]:91.0-96.2%)和93.9%(95%CI:90.6-96.1%),分别,3年和5年局部控制率分别为95.4%(95%CI:92.0-97.4%)和90.1%(95%CI:76.8-96.0%),分别。Meta回归分析显示,与三维适形放疗相比,PT与5年OS率显着相关(p<0.001)。在荟萃分析中使用的研究中,2级或更高的主要不良事件是颞叶坏死(发生率1-18%,中位数为7%)。
    PT治疗颅底软骨肉瘤具有良好的疗效,可能是放疗方式中一个有价值的选择。然而,颅底软骨肉瘤术后大剂量照射可引起颞叶坏死等不良事件。
    UNASSIGNED: Chondrosarcoma is a rare malignant bone tumor. Particle beam therapy (PT) can concentrate doses to targets while reducing adverse events. A meta-analysis based on a literature review was performed to examine the efficacy of PT and photon radiotherapy for skull base chondrosarcoma.
    UNASSIGNED: The meta-analysis was conducted using 21 articles published from 1990 to 2022.
    UNASSIGNED: After PT, the 3- and 5-year overall survival (OS) rates were 94.1% (95% confidence interval [CI]: 91.0-96.2%) and 93.9% (95% CI: 90.6-96.1%), respectively, and the 3- and 5-year local control rates were 95.4% (95% CI: 92.0-97.4%) and 90.1% (95% CI: 76.8-96.0%), respectively. Meta-regression analysis revealed a significant association of PT with a superior 5-year OS rate compared to three-dimensional conformal radiotherapy (p < 0.001). In the studies used in the meta-analysis, the major adverse event of grade 2 or higher was temporal lobe necrosis (incidence 1-18%, median 7%).
    UNASSIGNED: PT for skull base chondrosarcoma had a good outcome and may be a valuable option among radiotherapy modalities. However, high-dose postoperative irradiation of skull base chondrosarcoma can cause adverse events such as temporal lobe necrosis.
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  • 文章类型: Journal Article
    环境温度和细胞机械力是参与各种生物过程和调节癌症进展的固有因素,一直是全世界的热门话题。它们通过不同的方法在癌组织中占据主导地位。然而,关于致癌领域病理机制的广泛调查。经过研究,我们发现冷应激通过两种手段操纵肿瘤:神经科学和机械敏感离子通道(MICHs)如TRP家族来调节生理和病理活动。过度冷刺激介导的神经科学作用于每个癌症阶段,通过下丘脑-垂体-肾上腺皮质激素(HPA)到达靶器官。相对而言,通过MICHs压电的机械力控制癌症的发展。癌症的进展取决于原癌基因的内部激活和外部致瘤因素;上述两种手段最终导致分子水平的遗传疾病。本文就它们与肿瘤之间的双向交流相互作用作一综述。它涵盖了从细胞质到细胞核的主要过程,与转移级联和肿瘤免疫逃逸有关。
    Environmental temperature and cellular mechanical force are the inherent factors that participate in various biological processes and regulate cancer progress, which have been hot topics worldwide. They occupy a dominant part in the cancer tissues through different approaches. However, extensive investigation regarding pathological mechanisms in the carcinogenic field. After research, we found cold stress via two means to manipulate tumors: neuroscience and mechanically sensitive ion channels (MICHs) such as TRP families to regulate the physiological and pathological activities. Excessive cold stimulation mediated neuroscience acting on every cancer stage through the hypothalamus-pituitary-adrenocorticoid (HPA) to reach the target organs. Comparatively speaking, mechanical force via Piezo of MICHs controls cancer development. The progression of cancer depends on the internal activation of proto-oncogenes and the external tumorigenic factors; the above two means eventually lead to genetic disorders at the molecular level. This review summarizes the interaction of bidirectional communication between them and the tumor. It covers the main processes from cytoplasm to nucleus related to metastasis cascade and tumor immune escape.
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  • 文章类型: Journal Article
    SOX9是睾丸决定和发育的关键转录因子。SOX9基因及其周围的突变导致性发育(DSD)的差异/紊乱。然而,相当比例的DSD患者缺乏明确的基因诊断.SOX9靶基因是潜在的DSD致病基因,然而,在睾丸发育过程中只研究了这些基因的有限子集。我们假设SOX9靶基因在睾丸发育中起着不可或缺的作用,并且可能是DSD的致病基因。在这项研究中,我们描述了SOX9的一个新的睾丸靶基因Trpc3。在胚胎11.5天(E11.5)和E13.5之间,与小鼠胎儿性腺中的雌性颗粒细胞相比,Trpc3在表达SOX9的雄性支持细胞中表现出高表达水平。在XYSox9基因敲除性腺中,Trpc3表达显著下调。此外,用TRPC3抑制剂Pyr3培养E11.5XY小鼠性腺导致生殖细胞增殖减少导致生殖细胞数量减少。Trpc3也在内皮细胞中表达,Pyr3处理的E11.5XY小鼠性腺显示出由于内皮细胞凋亡增加而导致的体腔血管丢失。在人睾丸细胞系NT2/D1中,TRPC3促进细胞增殖并控制细胞形态,如xCELLigence和HoloMonitor实时分析所观察到的。总之,我们的研究表明,SOX9在小鼠睾丸中正向调节Trpc3,TRPC3可能在Sertoli期间介导SOX9功能,胚芽和内皮细胞发育。
    SOX9 is a key transcription factor for testis determination and development. Mutations in and around the SOX9 gene contribute to Differences/Disorders of Sex Development (DSD). However, a substantial proportion of DSD patients lack a definitive genetic diagnosis. SOX9 target genes are potentially DSD-causative genes, yet only a limited subset of these genes has been investigated during testis development. We hypothesize that SOX9 target genes play an integral role in testis development and could potentially be causative genes in DSD. In this study, we describe a novel testicular target gene of SOX9, Trpc3. Trpc3 exhibits high expression levels in the SOX9-expressing male Sertoli cells compared to female granulosa cells in mouse fetal gonads between embryonic day 11.5 (E11.5) and E13.5. In XY Sox9 knockout gonads, Trpc3 expression is markedly downregulated. Moreover, culture of E11.5 XY mouse gonads with TRPC3 inhibitor Pyr3 resulted in decreased germ cell numbers caused by reduced germ cell proliferation. Trpc3 is also expressed in endothelial cells and Pyr3-treated E11.5 XY mouse gonads showed a loss of the coelomic blood vessel due to increased apoptosis of endothelial cells. In the human testicular cell line NT2/D1, TRPC3 promotes cell proliferation and controls cell morphology, as observed by xCELLigence and HoloMonitor real-time analysis. In summary, our study suggests that SOX9 positively regulates Trpc3 in mouse testes and TRPC3 may mediate SOX9 function during Sertoli, germ and endothelial cell development.
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