RT Journal Article
SR Electronic
T1 MicroRNA-mediated Regulation of Mucin-type O-glycosylation Pathway: A Putative Mechanism of Salivary Gland Dysfunction in Sjögren Syndrome
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.180549
DO 10.3899/jrheum.180549
A1 Alessia Gallo
A1 Serena Vella
A1 Fabio Tuzzolino
A1 Nicola Cuscino
A1 Antonella Cecchettini
A1 Francesco Ferro
A1 Marta Mosca
A1 Ilias Alevizos
A1 Stefano Bombardieri
A1 Pier Giulio  Conaldi
A1 Chiara Baldini
YR 2019
UL http://www.jrheum.org/content/early/2019/08/08/jrheum.180549.abstract
AB Objective To investigate microRNA (miRNA) that is potentially implicated in primary Sjögren syndrome (pSS)–related salivary hypofunction in labial salivary glands and to study miRNA-mediated mechanisms underlying oral dryness and altered rheology, focusing on the mucin O-glycosylation pathway. Methods We performed miRNA expression profiling in minor salivary gland samples of patients with pSS presenting a different impairment in their unstimulated salivary flow rate. A computational in silico analysis was performed to identify genes and pathways that might be modulated by the deregulated miRNA that we had identified. To confirm in silico analysis, expression levels of genes encoding for glycosyltransferases and glycan-processing enzymes were investigated using Human Glycosylation-RT² Profiler PCR Array. Results Among 754 miRNA analyzed, we identified 126 miRNA that were significantly deregulated in pSS compared to controls, with a trend that was inversely proportional with the impairment of salivary flow rates. An in silico approach pinpointed that several upregulated miRNA in patients with pSS target important genes in the mucin O-glycosylation. We confirmed this prediction by quantitative real-time PCR, highlighting the downregulation of some glycosyltransferase and glycosidase genes in pSS samples compared to controls, such as GALNT1, responsible for mucin-7 glycosylation. Conclusion Collectively, our data suggest that the expression of different predicted miRNA-target genes in the mucin type O-glycan biosynthesis pathway is altered in pSS patients with low salivary flow and that the miRNA expression profile could influence the glycosidase expression levels and consequently the rheology in pSS.