Artículos de revistas
Type I interferon dependent hsa-miR-145-5p downregulation modulates MUC1 and TLR4 overexpression in salivary glands from sjögren’s syndrome patients
Fecha
2021Registro en:
Frontiers in Immunology June 2021 Volume 12 Article 685837
10.3389/fimmu.2021.685837
Autor
Jara, Daniela
Carvajal, Patricia
Castro Masso, Isabel Verónica
Barrera, María José
Aguilera, Sergio
González, Sergio
Molina, Claudio
Hermoso, Marcela Alejandra
González Burgos, María Antonieta
Institución
Resumen
Sjögren’s syndrome (SS) is an autoimmune disease that mainly affects salivary glands (SG)
and is characterized by overactivation of the type I interferon (IFN) pathway. Type I IFNs
can decrease the levels of hsa-miR-145-5p, a miRNA with anti-inflammatory roles that is
downregulated in SG from SS-patients. Two relevant targets of hsa-miR-145-5p, mucin 1
(MUC1) and toll-like receptor 4 (TLR4) are overexpressed in SS-patients and contribute to
SG inflammation and dysfunction. This study aimed to evaluate if hsa-miR-145-5p
modulates MUC1 and TLR4 overexpression in SG from SS-patients in a type I IFN
dependent manner. Labial SG (LSG) biopsies from 9 SS-patients and 6 controls were
analyzed. We determined hsa-miR-145-5p levels by TaqMan assays and the mRNA levels
of MUC1, TLR4, IFN-a, IFN-b, and IFN-stimulated genes (MX1, IFIT1, IFI44, and IFI44L) by
real time-PCR. We also performed in vitro assays using type I IFNs and chemically
synthesized hsa-miR-145-5p mimics and inhibitors. We validated the decreased hsamiR-
145-5p levels in LSG from SS-patients, which inversely correlated with the type I IFN
score, mRNA levels of IFN-b, MUC1, TLR4, and clinical parameters of SS-patients (Ro/La
autoantibodies and focus score). IFN-a or IFN-b stimulation downregulated hsa-miR-145-
5p and increased MUC1 and TLR4 mRNA levels. Hsa-miR-145-5p overexpression
decreased MUC1 and TLR4 mRNA levels, while transfection with a hsa-miR-145-5p
inhibitor increased mRNA levels. Our findings show that type I IFNs decrease hsa-miR-
145-5p expression leading to upregulation of MUC1 and TLR4. Together, this suggests
that type I interferon-dependent hsa-miR-145-5p downregulation contributes to the
perpetuation of inflammation in LSG from SS-patients.