新型肠道 NHE 亚型 (NHE8) 的调节-猫眼课题宝

新型肠道 NHE 亚型 (NHE8) 的调节

批准号：

8913142

负责人：

Fayez Khalaf Ghishan

金额：

$32.95万

依托单位：

UNIVERSITY OF ARIZONA

依托单位国家：

美国

项目类别：

财政年份：

2006

资助国家：

美国

项目状态：

已结题

起止时间：

2006-08-01 至 2017-08-31

来源：

https://reporter.nih.gov/project-details/8913142

关键词：

Acid-Base Equilibrium Acids Address Adult Age Animal Model Apical Architecture Bicarbonates Blood Brain Buffers Carbon Dioxide Carrier Proteins Cell Culture Techniques Cell physiology Chemistry Coupled Data Development Diet Down-Regulation Electrolytes Epidermal Growth Factor Epithelial Epithelial Cells Excision Eye Family Funding Gastric ulcer Gastrointestinal Contents Gastrointestinal tract structure Gene Expression Regulation Genes Glucocorticoids Goblet Cells Homeostasis Incidence Inflammatory disease of the intestine Injury Intervention Intestines Ions Kidney Kinetics Life Liquid substance Liver Male Genital Organs Male Sterility Measures Mitochondria Modeling Mucin-2 Staining Method Mucins Mus NHE2 Nutrient Pathology Pharmacologic Substance Phenotype Physiological Play Predisposition Process Production Protein Isoforms Public Health Refuse Disposal Regulation Reproductive Health Reproductive system Research Respiration Role SLC26A3 gene Source Sperm Capacitation Spermatogenesis Staging Sterility System Systems Development Testis Tissues Urine Volatile Fatty Acids Water absorption apical membrane base design fatty acid transport gastrointestinal gastrointestinal system insight leydig interstitial cell male meetings member novel postnatal putative anion transporter 1 reproductive reproductive development response wasting

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DESCRIPTION (provided by applicant): This is a competing renewal application designed to continue our studies on NHE8 (Na+/H+ exchanger isoform 8; SLC9A8), the newest member of a family of transport proteins involved in many cellular functions regulated through electroneutral Na+/H+ exchange. NHE8 is expressed in many tissues including the apical membrane of the epithelial cells in the intestine and the kidney. During the last funding period, we cloned NHE8 from the intestine and characterized its regulation during development. Furthermore, we showed that NHE8 plays a major role in apical Na+/H+ exchange during early life, and it compensates for the loss of NHE2 and NHE3 in NHE2-/-xNHE3-/- mice. We have developed a novel animal model of NHE8 deficiency and plan, in this renewal, to characterize the role of NHE8 in the gastrointestinal tract and the male reproductive system. Our central hypothesis is that NHE8 is essential for optimal HCO3- transport as evidenced by the down- regulation of DRA (down-regulated in adenoma; SLC26A3) and PAT1 (putative anion transporter 1, SLC26A6) in NHE8-/- mice. Because HCO3- is the byproduct of mitochondrial respiration and is essential for accelerating CO2 waste disposal, down regulation of HCO3- transport results in loss of control of cellular and systemic acid- base balance. Dysfunctional HCO3- transport is the basis of and a consequence of a variety of maladies. Based on the preliminary data obtained from phenotypic analysis of NHE8-/- mice, we have planned three specific aims to investigate the role of NHE8, the consequence of its loss on gastrointestinal and reproductive system development. The three specific aims are: 1) Phenotypic characterization of NHE8-/- mouse during development; 2) Characterization of the role of NHE8 in the gastrointestinal tract and in response to epithelial injury; and 3) Characterization of the role of NHE8 in testicular function. The studies are novel and will yield new insight into the role of NHE8 to include regulation of ion fluxes in epithelial cells in general.

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