miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p

• Main Authors: Sara Bozzini, Laura Pandolfi, Elena Rossi, Simona Inghilleri, Michele Zorzetto, Giuseppina Ferrario, Stefano Di Carlo, Gianfranco Politano, Annalisa De Silvestri, Vanessa Frangipane, Michele Porzio, Romain Kessler, Fiorella Calabrese, Federica Meloni, Patrizia Morbini
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Cells
• Subjects: chronic lung allograft dysfunction; bronchiolitis obliterans; microRNA; miR-21-5p; in situ hybridization
• Online Access: https://www.mdpi.com/2073-4409/10/3/688

Epigenetic changes, including miRNAs deregulation, have been suggested to play a significant role in development of obliterative bronchiolitis (OB) in transplanted lungs. Many studies have tried to identify ideal candidate miRNAs and the downstream pathways implicated in the bronchiolar fibro-obliterative process. Several candidate miRNAs, previously indicated as possibly being associated with OB, were analyzed by combining the quantitative real time-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) of lung tissues of OB affected patients. Disease- and OB-lesion-specific expression of miR-21-5p was confirmed by computational analyses and we were able to identify the network of genes most probably associated miR-21-5p in the context of OB fibrogenesis. Among all potentially associated genes, STAT3 had a very high probability score. Immunohistochemistry showed that STAT3/miR-21-5p were co-over expressed in OB lesions, thus, suggesting miR-21-5p could regulate STAT3 expression. However, miR-21-5p inhibition in cultures of bronchiolitis obliterans syndrome (BOS) derived myofibroblasts did not significantly affect STAT3 mRNA and protein expression levels. This study demonstrates the specificity of miR-21-5p over-expression in OB lesions and contributes to existing knowledge on the miR-21-5p downstream pathway. Activation of STAT3 is associated with miR-21-5p upregulation, however, STAT-3 network activation is most likely complex and miR-21-5p is not the sole regulator of STAT3.