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Abstract
Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.
Acknowledgments
We thank all local residents and patients who participated in the study. We thank all local doctors, especially Junsheng Zhang, Hailing Ruan, Jinzhi Tang, and Jun Zhan for the help of the investigation.
Disclosure Statement
All authors report no conflicts of interest.
Additional information
Funding
Notes on contributors
Hanhan Wu
Anla Hu: Conceptualization, Methodology, Supervision, Writing-Original Draft, Funding acquisition. Hanhan Wu: Writing-Original Draft, Formal analysis, Investigation. Didi Zhao: Data Curation, Writing-Original Draft, Investigation. Chen Wang: Investigation, Data Curation, Methodology. Daoming Zhang: Investigation, Supervision. Min Tang: Investigation, Supervision. Shiqing Qian: Investigation, Supervision. Lina Xu: Investigation. Tao Xia: Investigation. Juanyan Zhou: Investigation. Guangjun Wang: Investigation. Yue He: Investigation. Lei Gao: Investigation. Wenjun Chen: Methodology, Supervision. Li Li: Conceptualization, Supervision. Wanshui Yang: Methodology, Supervision. Qihong Zhao: Investigation, Funding acquisition. Chuanlai Hu: Conceptualization. All authors had read and approved the final draft.