SLC9A4

更新于：2025-05-07

基本信息

别名

Na(+)/H(+) exchanger 4、NHE-4、NHE4

+ [7]

简介

Electroneutral antiporter that exchanges sodium for protons or ammonium ions at the basolateral membrane of epithelia to regulate cell volume and intracellular pH upon hypertonic conditions (By similarity). As part of transcellular ammonia transport in renal tubules, mediates basolateral ammonium extrusion in the medullary thick ascending limb, regulating the corticopapillary ammonium gradient and overall renal acid excretion (By similarity). Mediates sodium:proton exchange in gastric parietal cells secondary to cAMP-dependent acid secretion and hyperosmolarity. Possibly coupled to chloride:bicarbonate antiporter, enables loading of parietal cells with sodium and chloride ions to maintain cell volume and normal gastric acid secretion (By similarity). Functions as a sodium sensor in neurons of organum vasculosum of the lamina terminalis where it regulates water intake in response to increased sodium concentration in body fluids (By similarity).

关联

项与 SLC9A4 相关的药物

d9A-2

靶点

NHE1 x NHE2 x SLC9A4 x SLC9A7 x SLC9B1

作用机制

NHE1抑制剂 [+4]

在研机构-

原研机构

Das CeMM - Forschungszentrum für Molekulare Medizin GmbH

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SLC9A4 相关的临床结果

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100 项与 SLC9A4 相关的转化医学

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0 项与 SLC9A4 相关的专利（医药）

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101

项与 SLC9A4 相关的文献（医药）

2024-06-01·Annals of the American Thoracic Society

Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19

Article

作者: Palotie, Aarno ; Strausz, Satu ; Bachour, Adel ; Tiullinen, Varvara ; Broberg, Martin ; Ripatti, Samuli ; Ollila, Hanna M ; Koskela, Jukka ; Gottlieb, Daniel J ; Agafonova, Elizabete ; Sofer, Tamar ; Ruotsalainen, Sanni E ; Palotie, Tuula ; Kiiskinen, Tuomo

Rationale: Although patients with obstructive sleep apnea (OSA) have a higher risk for coronavirus disease (COVID-19) hospitalization, the causal relationship has remained unexplored. Objectives: To understand the causal relationship between OSA and COVID-19 by leveraging data from vaccination and electronic health records, genetic risk factors from genome-wide association studies, and Mendelian randomization. Methods: We elucidated genetic risk factors for OSA using FinnGen (total N = 377,277), performing genome-wide association. We used the associated variants as instruments for univariate and multivariate Mendelian randomization (MR) analyses and computed absolute risk reduction against COVID-19 hospitalization with or without vaccination. Results: We identified nine novel loci for OSA and replicated our findings in the Million Veteran Program. Furthermore, MR analysis showed that OSA was a causal risk factor for severe COVID-19 (P = 9.41 × 10^-4). Probabilistic modeling showed that the strongest genetic risk factor for OSA at the FTO locus reflected a signal of higher body mass index (BMI), whereas BMI-independent association was seen with the earlier reported SLC9A4 locus and a MECOM locus, which is a transcriptional regulator with 210-fold enrichment in the Finnish population. Similarly, multivariate MR analysis showed that the causality for severe COVID-19 was driven by BMI (multivariate MR P = 5.97 × 10^-6, β = 0.47). Finally, vaccination reduced the risk for COVID-19 hospitalization more in the patients with OSA than in the non-OSA controls, with respective absolute risk reductions of 13.3% versus 6.3%. Conclusions: Our analysis identified novel genetic risk factors for OSA and showed that OSA is a causal risk factor for severe COVID-19. The effect is predominantly explained by higher BMI and suggests BMI-dependent effects at the level of individual variants and at the level of comorbid causality.

2024-06-01·Heliyon

Baicalin-aluminum complex on the regulation of IPEC-1 infected with enterotoxigenic Escherichia coli

Article

作者: Zhao, Ming ; Liu, Yu ; Qiu, Yinsheng ; Wu, Zhongyuan ; Chen, Yuqian ; Yu, Ruixue ; Fu, Shulin ; Yin, Ronghua ; Ye, Chun

Enterotoxigenic Escherichia coli (ETEC) is the main bacterial cause of diarrhea in weaned piglets. Baicalin-aluminum (BA) complex is the main active ingredient of Scutellaria baicalensis Georgi extracted-aluminum complex, which has been used to treat diarrhea in weaning piglets, however the underlying mechanism remains unclear. To investigate the effects of the BA complex on the regulation of porcine intestinal epithelial (IPEC-1) cells infected with ETEC, IPEC-1 cells were incubated with an ETEC bacterial strain at a multiplicity of infection of 1 for 6 h and then treated with different concentrations of the BA complex for 6 h. ETEC infection increased the levels of cAMP and cGMP, upregulated CFTR (cystic fibrosis transmembrane conductance regulator) mRNA, and downregulated NHE4 mRNA in IPEC-1 cells. Treatment with the BA complex inhibited ETEC adhesion and the production of cAMP and cGMP, reduced CFTR mRNA expression, and increased NHE4 mRNA expression. Overall, the BA complex weakened the adhesion of ETEC to IPEC-1 cells, and inhibited cAMP/cGMP-CFTR signaling in IPEC-1 cells.

2023-03-01·3 Biotech

Genome-wide association study revealed suggestive QTLs for production and reproduction traits in Indian Murrah buffalo

Article

作者: Gupta, I D ; Nandhini, P B ; Ravi Kumar, D ; Mengistu, Destaw Worku ; Joel Devadasan, M ; Tantia, M S ; Sivalingam, Jayakumar ; Kataria, R S ; Niranjan, S K ; Verma, Archana

The present study was aimed to identify the genome-wide SNPs associated with production and reproduction traits in 96 Indian Murrah buffalo genotyped based on ddRAD approach using Genome-Wide Association Study (GWAS) along with phenotypes of contemporary animals using mixed linear model for production and reproduction traits. A total of 27,735 SNPs identified using ddRAD approach in 96 Indian Murrah buffaloes were used for GWAS. A total of 28 SNPs were found to be associated with production and reproductive traits. Among these, 14 SNPs were present in the intronic region of AK5, BACH2, DIRC2, ECPAS, MPZL1, MYO16, QRFPR, RASGRF1, SLC9A4, TANC1, and TRIM67 genes and one SNP in long non-coding region of LOC102414911. Out of these 28 SNPs, 9 SNPs were found to have pleiotropic effect over milk production traits and were present in chromosome number BBU 1, 2, 4, 6, 9, 10, 12, 19, and 20. SNPs in the intronic region of AK5, TRIM67 genes were found to be associated with milk production traits. Eleven and five SNPs in the intergenic region were associated with milk production and reproduction traits respectively. The above genomic information may be used for selection of Murrah animals for genetic improvement.

项与 SLC9A4 相关的新闻（医药）

2024-11-25

·生物谷

慢性肾病（Chronic Kidney Disease, CKD）是全球致死和致残的重要原因之一。由于CKD通常与一系列不良健康结局相关，如心血管疾病和早逝，因此早期预防至关重要。近年来，心理社会因素与CKD之间的潜在关联受到广泛关注，然而不同阶段的不良生活事件暴露如何影响CKD的发病机制尚不清楚。近日，四川大学曾筱茜研究团队在Transl Psychiatry发表了题为The association between patterns of exposure to adverse life events and the risk of chronic kidney disease: a prospective cohort study of 140,997 individuals的研究论文。研究发现，贯穿童年至成年的不良生活事件会显著增加慢性肾病的发病风险，且BMI（体重指数）、吸烟和高血压是该关联的主要中介因素。基因-环境相互作用分析揭示了炎症通路在这一过程中发挥关键作用，提示心理社会因素对慢性肾病预防的重要性。研究方法本研究使用了来自英国生物样本库的数据，纳入了140,997名完成心理健康问卷的参与者。通过童年虐待、成年期逆境和灾难性创伤三大领域的15个调查项目，进行潜在类别分析（LCA），以识别不同模式的不良生活事件暴露。最终确定了五类暴露模式，分别为：“低水平暴露”、“童年暴露”、“成年暴露”、“性虐待”和“从童年至成年的暴露”。CKD的发病通过国际疾病分类（ICD）代码识别，并使用Cox比例风险回归模型分析各暴露模式与CKD之间的关联。结果与讨论 1. 不良生活事件与CKD的总体关联在中位随访5.98年（合计843,232.5人年）期间，共有2734名参与者被诊断为新发CKD，发病率为1.94%，即每1000人年发病率为3.24例。通过Cox比例风险回归模型，研究首先评估了三大领域的不良生活事件（童年虐待、成年期逆境和灾难性创伤）分别与CKD发病风险的关联。结果显示，童年虐待与CKD的发病风险显著相关（HR 1.10, 95% CI 1.002–1.21, P<0.001），而成年期逆境和灾难性创伤则未显示出显著的关联。图 1：不良生活事件暴露模式与新发CKD发展的关联 2. 不同暴露模式的影响进一步的分析表明，与“低水平暴露”相比，“从童年至成年的暴露”模式显著增加了CKD的发病风险（HR 1.37, 95% CI 1.14–1.65, P<0.001）。这一模式中，参与者在童年和成年期都经历了多种不良事件，表明持续性的创伤暴露对肾功能有深远影响。这一结果与已有研究表明的不良生活事件对心血管疾病、糖尿病等慢性疾病的影响相一致，进一步拓展了不良生活事件对肾脏健康影响的证据。其他暴露模式，如“童年暴露”、“成年暴露”和“性虐待”，未显示出与CKD发病的显著关联。这可能表明，单一时期的不良事件暴露对CKD的影响较弱，而贯穿童年到成年期的长期创伤累积可能是CKD发病的关键因素。图 2：不同亚组中不良生活事件暴露模式与新发CKD发展的关联 3. 性别、年龄及遗传风险的调节作用在亚组分析中，研究发现，“从童年至成年的暴露”模式对女性、65岁以下人群及肾功能下降的遗传风险较低的个体影响更为显著。研究人员指出，女性在应对不良生活事件方面的生理和心理机制可能与男性不同，表现出更高的心理应激和生理反应。此外，年龄和遗传背景也会调节不良生活事件对健康的影响。与低遗传风险个体相比，具有较高遗传风险的个体可能更容易受到其他健康因素（如糖尿病、高血压等）的影响，从而使不良生活事件对CKD的独立贡献减弱。 4. 中介分析：BMI、吸烟与高血压的影响中介分析进一步揭示了BMI、吸烟和高血压在不良生活事件与CKD发病之间的重要作用。 BMI中介了11.45%的总效应，吸烟中介了9.79%，高血压中介了4.50%。这表明，不良生活事件可能通过增加肥胖、吸烟和高血压等已知的CKD风险因素，间接促进了CKD的发生。相较之下，饮食和糖尿病的中介作用未显示显著结果。图 3：“儿童到成年暴露”模式与慢性肾病关联的中介作用 5. 基因-环境相互作用基因-环境相互作用研究（GEWIS）识别出154个与“从童年至成年的暴露”模式交互的SNP（单核苷酸多态性）位点，这些位点主要富集于炎症通路，尤其是与白介素1受体和细胞因子受体活性相关的基因。进一步的功能注释分析表明，SNP rs11676124可能通过调控SLC9A4基因的表达，参与肾脏疾病的发病过程。SLC9A4基因与白介素1受体样蛋白（IL1R1）的水平相关，后者已被证实在CKD的促炎反应中起关键作用。这一发现为不良生活事件通过炎症机制影响CKD提供了新的证据。图 4：不同基因多态性个体暴露于不良生活事件模式与新发CKD发展的关联结论本研究首次揭示了不良生活事件暴露模式与CKD风险之间的显著关联，研究表明，贯穿童年至成年的不良生活事件显著增加了慢性肾病的发病风险，BMI、吸烟和高血压是这一关联的重要中介因素。此外，基因-环境相互作用分析揭示了可能的分子机制，表明炎症通路在不良生活事件引发CKD过程中起重要作用。建议可将心理社会因素纳入CKD的精准预防和早期干预策略中。参考文献： Li, C., Chen, J., Chen, Y. et al. The association between patterns of exposure to adverse life events and the risk of chronic kidney disease: a prospective cohort study of 140,997 individuals. Transl Psychiatry 14, 424 (2024). https://doi.org/10.1038/s41398-024-03114-4 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~

临床研究临床终止