Extracellular vesicle microRNAs in celiac disease patients under a gluten-free diet, and in lactose intolerant individuals

无麸质饮食的乳糜泻患者和乳糖不耐症患者的细胞外囊泡微小RNA

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作者:Débora S Lemos, Helen C Beckert, Luana C Oliveira, Fernanda C B Berti, Patricia M M Ozawa, Ingrid L M Souza, Silvio M Zanata, Vânia C S Pankievicz, Thalita R Tuleski, Emanuel M Souza, Rosiane V Silva, Pryscilla F Wowk, Maria Luiza Petzl-Erler, Rodrigo C Almeida, Gabriel Adelman Cipolla, Angelica B W

Aims

To identify altered extracellular vesicle miRNAs from plasma among CD patients on GFD (n=34), lactose intolerant individuals on restrictive diet (n=14) and controls (n=23), and to predict biological pathways in which these altered miRNAs may play a part.

Background

Celiac disease (CD) is an autoimmune disorder triggered by an abnormal immunological response to gluten ingestion and is associated with deregulated expression of cellular microRNAs (miRNAs) of the gut mucosa. It is frequently misdiagnosed as lactose intolerance (LI) due to symptom resemblance. Microvilli loss may be counteracted by a rigorous gluten-free diet (GFD). Aims: To identify altered extracellular vesicle miRNAs from plasma among CD patients on GFD (n=34), lactose intolerant individuals on restrictive diet (n=14) and controls (n=23), and to predict biological pathways in which these altered miRNAs may play a part.

Conclusions

These miRNAs may have targets that affect cell death, cell communication, adhesion, and inflammation modulation pathways. Hence, altered miRNA levels could be associated with CD-related aspects and gut mucosa recovery.

Methods

Five different small RNA samples of each group were pooled twice and then screened by new-generation sequencing. Four miRNAs were selected to be quantified by RT-qPCR in the entire sample.

Results

The levels of four miRNAs - miR-99b-3p, miR-197-3p, miR-223-3p, and miR-374b-5p - differed between CD patients and controls (P<0.05). Apart from miR-223-3p, all these miRNAs tended to have altered levels also between LI and controls (P<0.10). The results for miR-99b-3p and miR-197-3p between CD and controls were confirmed by RT-qPCR, which also indicated different levels of miR-99b-3p and miR-374b-5p between CD-associated LI and LI (P<0.05). Conclusions: These miRNAs may have targets that affect cell death, cell communication, adhesion, and inflammation modulation pathways. Hence, altered miRNA levels could be associated with CD-related aspects and gut mucosa recovery.

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