Version 1
: Received: 6 November 2023 / Approved: 7 November 2023 / Online: 7 November 2023 (11:36:58 CET)
How to cite:
Vargas-Castro, R.; Olmos-Ortiz, A.; García-Quiroz, J.; Avila, E.; Larrea, F.; Díaz, L. Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta. Preprints2023, 2023110402. https://doi.org/10.20944/preprints202311.0402.v1
Vargas-Castro, R.; Olmos-Ortiz, A.; García-Quiroz, J.; Avila, E.; Larrea, F.; Díaz, L. Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta. Preprints 2023, 2023110402. https://doi.org/10.20944/preprints202311.0402.v1
Vargas-Castro, R.; Olmos-Ortiz, A.; García-Quiroz, J.; Avila, E.; Larrea, F.; Díaz, L. Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta. Preprints2023, 2023110402. https://doi.org/10.20944/preprints202311.0402.v1
APA Style
Vargas-Castro, R., Olmos-Ortiz, A., García-Quiroz, J., Avila, E., Larrea, F., & Díaz, L. (2023). Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta. Preprints. https://doi.org/10.20944/preprints202311.0402.v1
Chicago/Turabian Style
Vargas-Castro, R., Fernando Larrea and Lorenza Díaz. 2023 "Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta" Preprints. https://doi.org/10.20944/preprints202311.0402.v1
Abstract
Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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