Allele specific expression of TAS2R38 in human taste and nasal tissue

TAS2R38 在人类味觉和鼻组织中的等位基因特异性表达

• 批准号: 8823914
• 负责人: Noam A Cohen
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8823914
• 关键词: 21 year old; Accounting; Affect; Agonist; Air; Alleles; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biological Assay; Biological Process; Blood typing procedure; Cells; Chronic; Cilia; Clinical; Data; Defense Mechanisms; Diffuse; Disease; Epithelial; Epithelial Cells; Epithelium; Exposure to; Frequencies; Fungiform Papilla; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Gram-Negative Bacteria; Growth; Health; Heterozygote; Human; Immune response; In Vitro; Individual; Infection; Inflammation; Ligands; Link; Liquid substance; Measures; Messenger RNA; Mucociliary Clearance; Mucous body substance; Nasal Epithelium; Nitric Oxide; Nose; Operative Surgical Procedures; Patients; Perception; Persons; Phenylthiourea; Population; Population Density; Process; Production; Pseudomonas aeruginosa; Receptor Gene; Research; Resected; Residual state; Risk; Saliva; Sampling; Severities; Solutions; Structure of mucous membrane of nose; Study Subject; Taste Buds; Taste Perception; Testing; Therapeutic; Therapeutic Intervention; Tissue Sample; Tissues; Tongue; Variant; Virulence; base; clinical material; homoserine lactone; innate immune function; killings; public health relevance; quorum sensing; receptor; receptor expression; receptor function; research study; respiratory; response; taste system; trait

DESCRIPTION (provided by applicant): The human taste system may provide a window on human health. We have recently demonstrated that the bitter taste receptor T2R38 is expressed in the upper airway and is activated by acyl-homoserine lactones (AHLs): quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Furthermore, we found that T2R38 regulates human upper airway innate defenses through nitric oxide (NO) production, which stimulates mucociliary clearance and has direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene which confer functionality of the receptor, correlate with taste sensitivity to the molecule PTC are linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria in response to AHL. There are three common genotypes for this gene, homozygous dominant, homozygous recessive and heterozygotes. The greatest degree of variability in both PTC taste perception and AHL induced respiratory defense are found in the heterozygote population. Our hypothesis is that allele specific expression of the TAS2R38 polymorphisms predict its function in taste and sinonasal tissue. To test this hypothesis we will collect fungiform taste and sinonasal tissue from 25 heterozygote patients undergoing sinonasal surgery for use in two specific aims: (1) to assess allele specific expression from the sinonasal epithelium and determine whether this persists as the cells are grown in vitro as air liquid interface cultures and correlates to AHL induced respiratory defenses and (2) assess allele specific expression in the fungiform papillae and determine whether it correlates with PTC bitter taste perception and the allele specific expression in the nose. The goal of these aims is to better understand the relationship of the functional and non-functional variants of the TAS2R38 gene in two distinct systems, taste and respiratory defense, and determine whether taste perception can be used clinically to predict severity of airway infection.

描述（由申请人提供）：人类味觉系统可以为人类健康提供一个窗口。我们最近已经证明，苦味受体T2R38在上呼吸道表达，并激活酰基高丝氨酸内酯（AHLs）：由铜绿假单胞菌和其他革兰氏阴性菌分泌的群体感应分子。此外，我们发现T2R38通过一氧化氮（NO）的产生调节人类上呼吸道的先天防御，这刺激粘膜纤毛清除并具有直接的抗菌作用。此外，TAS2R38基因的常见多态性赋予受体的功能性，与对分子PTC的味觉敏感性相关，与上呼吸道细胞响应阿勒清除和杀死细菌的能力的显著差异有关。该基因有三种常见的基因型，纯合显性、纯合隐性和杂合子。PTC味觉和阿勒诱导的呼吸防御的最大程度的变异被发现在杂合子人群。我们的假设是TAS2R38多态性的等位基因特异性表达预测其在味觉和鼻窦组织中的功能。为了验证这一假设，我们将收集真菌样味觉和鼻窦组织， 25例杂合子患者接受鼻窦手术，用于两个特定目的：（1）评估来自鼻窦上皮的等位基因特异性表达，并确定当细胞作为气液界面培养物在体外生长时，这种表达是否持续，并与阿勒诱导的呼吸防御相关，以及（2）评估菌状乳头中的等位基因特异性表达，并确定其是否与PTC苦味感知和鼻中的等位基因特异性表达相关。这些目标的目的是更好地了解TAS 2R38基因的功能性和非功能性变体在味觉和呼吸防御这两个不同系统中的关系，并确定味觉是否可以在临床上用于预测气道感染的严重程度。