The Clinical Significance Of ASAP3 Protein And Association With Human Gastric Acidity

Objectives:This study aimed to investigate the expression of ASAP3 protein in gastric parietal cells,revealed the relationship with gastric acidity or acid-related disease,and discussed the underlying mechanism,further explored new method of gastric acid inhibition by targeting ASAP3.Methods:90 specimens were obtained randomly from patients who underwent gastroscopy in the Division of Gastroenterology and Hepatology,Shanghai Renji Hospital during Dec 1,2013 to Dec 31,2014.Immunofluorescence staining was used to observe the distribution features of ASAP3 protein in gastric body mucosa.ASAP3 level and the relationship between the gastric acidity were measured by immunohistochemical staining and neutralization titration,and further investigated the relation between ASAP3 and upper gastrointestinal diseases according to gastroscope diagnoses and pathological diagnoses.The ASAP3 inhibitor QS11 was administrated to wild type mice by intraperitoneal injection to testify the impact of ASAP3 on acid secretion.Results:Compared with interstitial cells and other cells in oxyntic gland,ASAP3 was mainly expressed in parietal cells.Low expression of ASAP3 was accompanied with less H,K-ATPase distribution among apical membrane.ASAP3 level was strongly correlated with gastric acidity(R=0.615,P<0.001).Furthermore,patients with gastroesophageal reflux disease have significantly higher ASAP3 expression level(P<0.05).In addition,prevalence rate of gastric ulcer significantly rose in patients with a high level of ASAP3(P=0.022).ASAP3 and no significant relation with pathological changes of gastric mucosal such as chronic inflammation,atrophy,intestinal metaplasia or history of Helicobacter pylori infection.In vivo administration of QS11 exhibited significant decrease in gastric acidity.Conclusion:Our results indicated that ASAP3 expression level in the parietal cell influence the distribution of H,K-ATPase.ASAP3 was strongly correlated with gastric acidity,thus ASAP3 could reflect acid secreting condition in gastric.ASAP3 was closely associated with gastric ulcer and gastroesophageal reflux disease,meanwhile,the expression was hardly affected by pathological changes in gastric mucosa.Therefore ASAP3 might contribute to the risk assessment of the acid-related diseases.Inhibition of ASAP3 significantly reduced gastric acid secretion.These findings not only enriched understanding of the physiological function of ASAP3,also provide a potential therapeutic targets for acid suppression.