Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19

Author:

Ammirata Giorgia1,Arigoni Maddalena1,Licastro Danilo2,Caviglia Gian Paolo3ORCID,Disabato Michela3,Zubair Ghania4,Bezzio Cristina56ORCID,Saibeni Simone7ORCID,De Nicolò Amedeo8ORCID,Cusato Jessica8ORCID,Palermiti Alice8ORCID,Manca Alessandra8ORCID,Tolosano Emanuela1ORCID,Cozzini Stefano2,Mancini Marcello9,Altruda Fiorella1ORCID,D’Avolio Antonio8ORCID,Ribaldone Davide Giuseppe3ORCID,Ala Ugo10ORCID,Fagoonee Sharmila11ORCID

Affiliation:

1. Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre “Guido Tarone”, University of Turin, 10126 Turin, Italy

2. AREA Science Park, Padriciano, 34149 Trieste, Italy

3. Gastroenterology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy

4. Department of Mathematics “Giuseppe Peano”, University of Turin, 10126 Turin, Italy

5. IBD Centre, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy

6. Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy

7. Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Milan, Italy

8. Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy

9. Institute for Biostructure and Bioimaging, CNR, Via T. De Amicis 95, 80145 Naples, Italy

10. Department of Veterinary Sciences, University of Turin, Grugliasco, 10095 Turin, Italy

11. Institute for Biostructure and Bioimaging, CNR, Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy

Abstract

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection.

Funder

Area Science Park and Piattaforma di Genomica del Sistema ARGO with the support of Regione Autonoma Friuli Venezia Giulia, Ministry of University and Research and Ministry of Economic development

Ricerca Locale—Linea A—Department of Veterinary Sciences, University of Torino

Publisher

MDPI AG

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