A García-Sánchez1,2, E Marcos-Vadillo2,3, C Sanz2,4, L Hernández-Hernández2, G Cerutti-Müller5, F Marqués-García2,3, F Lorente6,2,7, M Isidoro-García2,3,8, I Dávila6,2,9. 1. 1Department of Biomedical and Diagnostic Science, University of Salamanca, Salamanca, Spain. 2. Biomedical Research Institute of Salamanca, IBSAL, Salamanca, Spain. 3. Department of Clinical Biochemistry, Salamanca University Hospital, Salamanca, Spain. 4. Department of Microbiology and Genetics, University of Salamanca, Spain. 5. Universidade do Vale do Rio dos Sinos-UNISINOS, São Leopoldo, Brazil. 6. Department of Biomedical and Diagnostic Science, University of Salamanca, Salamanca, Spain. 7. Department of Pediatrics, Salamanca University Hospital, Salamanca, Spain. 8. Department of Medicine, University of Salamanca, Salamanca, Spain. 9. Department of Immunoallergy, Salamanca University Hospital, Salamanca, Spain.
Abstract
BACKGROUND AND OBJECTIVE: Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was to analyze the effect of RA on the activation of the promoter region of the PTGDR gene. METHODS: A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all-trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG, and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis. RESULTS: After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region. CONCLUSIONS: RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmatic patients.
BACKGROUND AND OBJECTIVE:Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was to analyze the effect of RA on the activation of the promoter region of the PTGDR gene. METHODS: A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all-trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG, and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis. RESULTS: After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region. CONCLUSIONS:RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmaticpatients.
Authors: Yi Zhou; Zhi-Sheng Liang; Yinzi Jin; Jiayuan Ding; Tao Huang; Jason H Moore; Zhi-Jie Zheng; Jie Huang Journal: Front Genet Date: 2022-01-20 Impact factor: 4.599