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

Abstract

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.

Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis

“…Many studies have tried to identify miRNA ideal candidate, and the downstream pathways implicated in the bronchiolar fibro-obliterative process [17]. Different studies evaluated the immunomodulatory effect of ECP therapy in patients after solid organ transplant rejection [18][19][20][21][22], but few studies have explored the molecular regulation associated with ECP treatment [12].…”

Aplicaciones clínicas de miR-21: revisión de la literatura

“…En pacientes con trasplante de pulmón se observó una correlación entre la sobreexpresión de miR-21 y el proceso fibro-obliterativo de múltiples trastornos involucrados con fibrosis, entre ellos la disfunción crónica de aloinjerto pulmonar, enfermedad que limita la supervivencia de pacientes trasplantados. El aumento en la expresión de miR-21 suele preceder la instauración de síndrome de bronquiolitis obliterante, lo que alienta a continuar su estudio en esta patología (30).…”

Molecular monitoring of lung allograft health: is it ready for routine clinical use?

“…Several studies have attempted to identify specific miRNAs associated with CLAD development, with pro-fibrotic miRNA-21 being the most promising candidate [70][71][72]. Its co-over expression with signal transducer and activator of transcription 3 could play a role in the development of obliterative bronchiolitis [73]. In a small pilot study, miRNA-21 showed a good discriminative power (AUC of 0.89) in confirming a CLAD diagnosis.…”