MIRNAS POTENTIALLY INVOLVED IN POST LUNG TRANSPLANT-OBLITERATIVE BRONCHIOLITIS: THE ROLE OF MIR-21-5P

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

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

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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 transpharm online shopping 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 and by computational analysis 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 napoleon concealer 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.

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