Modulation of microRNome by Human Cytomegalovirus and Human Herpesvirus 6 Infection in Human Dermal Fibroblasts: Possible Significance in the Induction of Fibrosis in Systemic Sclerosis

Cells

Irene Soffritti¹  Maria D’Accolti¹  Elisabetta Caselli¹  FloraDe Conto²  Clara Maccari²  Adriana Calderaro²  Maria-Cristina Arcangeletti²  Gloria Ravegnini³ 

[1] Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy;Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy;Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy;

关键词: microRNA;    miRNome;    human cytomegalovirus;    human herpesvirus 6;    systemic sclerosis;    fibrosis;   

DOI  :  10.3390/cells10051060

来源: DOAJ

【 摘 要 】

Human cytomegalovirus (HCMV) and Human herpesvirus 6 (HHV-6) have been reportedly suggested as triggers of the onset and/or progression of systemic sclerosis (SSc), a severe autoimmune disorder characterized by multi-organ fibrosis. The etiology and pathogenesis of SSc are still largely unknown but virological and immunological observations support a role for these beta-herpesviruses, and we recently observed a direct impact of HCMV and HHV-6 infection on the expression of cell factors associated with fibrosis at the cell level. Since miRNA expression has been found profoundly deregulated at the tissue level, here we aimed to investigate the impact on cell microRNome (miRNome) of HCMV and HHV-6 infection in in vitro infected primary human dermal fibroblasts, which represent one of the main SSc target cells. The analysis, performed by Taqman arrays detecting and quantifying 754 microRNAs (miRNAs), showed that both herpesviruses significantly modulated miRNA expression in infected cells, with evident early and late effects and deep modulation (>10 fold) of >40 miRNAs at each time post infection, including those previously recognized for their key function in fibrosis. The correlation between these in vitro results with in vivo observations is strongly suggestive of a role of HCMV and/or HHV-6 in the multistep pathogenesis of fibrosis in SSc and in the induction of fibrosis-signaling pathways finally leading to tissue fibrosis. The identification of specific miRNAs may open the way to their use as biomarkers for SSc diagnosis, assessment of disease progression and possible antifibrotic therapies.

【 授权许可】

Unknown