ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2017
Significant role for microRNA-21 affecting toll-like receptor pathway in primary graft dysfunction after human lung transplantation.
Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Primary graft dysfunction after Lung transplantation: unveiling the role of innate immunity.Clinical and experimental immunology · 2025Article
- Advances in lung ischemia/reperfusion injury: unraveling the role of innate immunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- MiRNA-122 Promotes Ischemia-Reperfusion Injury after Lung Transplantation via the Toll-like Receptor Signaling Pathway.Current medical science · 2021Article
- Emerging roles of microRNAs in the regulation of Toll-like receptor (TLR)-signaling.Frontiers in bioscience (Landmark edition) · 2021Article
- International Society for Heart and Lung Transplantation consensus statement for the standardization of bronchoalveolar lavage in lung transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2020Article
- The role of innate immunity in the long-term outcome of lung transplantation.Annals of translational medicine · 2020Review
- miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling.International journal of molecular sciences · 2020Article
- Long non-coding RNA X-inactive specific transcript silencing ameliorates primary graft dysfunction following lung transplantation through microRNA-21-dependent mechanism.EBioMedicine · 2020Article
- Serum miR-222-3p as a Double-Edged Sword in Predicting Efficacy and Trastuzumab-Induced Cardiotoxicity for HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Target Therapy.Frontiers in oncology · 2020Article
- DPP-4 inhibition by linagliptin prevents cardiac dysfunction and inflammation by targeting the Nlrp3/ASC inflammasome.Basic research in cardiology · 2019Article
- The Interaction Between Two Worlds: MicroRNAs and Toll-Like Receptors.Frontiers in immunology · 2019Review
- Applying genomics in heart transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2018Review
- Pathophysiology and classification of primary graft dysfunction after lung transplantation.Journal of thoracic disease · 2017Review
- Transplant genetics and genomics.Nature reviews. Genetics · 2017Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMicroRNAs (miRNAs) were recently identified as modulators of immune responses after human lung transplantation (LTx). This study was undertaken to assess the contribution of miRNAs to the pathogenesis of primary graft dysfunction (PGD) after LTx.
methodsOf the 39 recipients, 14 (35.9%) developed Grade 3 PGD (i.e., severe PGD) within the first 72 hours of LTx. The remaining 25 recipients (64.1%) had Grade 2 or less PGD, and served as the control group. miRNAs were isolated from cells purified by bronchoalveolar lavage (BAL). Bioinformatic prediction and validation by luciferase reporter assays were performed to identify targets regulated by miR-21. Transfection of human monocytic cell line (THP-1) was conducted to determine miR-21's cellular function.
resultsPilot miRNA profiling of donor BAL samples before implantation in PGD (n = 6) revealed significant upregulation in 44 miRNAs and downregulation in 80 miRNAs compared with control (n = 6). Validation using a separate cohort demonstrated significant underexpression of miR-21 in patients with severe PGD. Furthermore, underexpression of miR-21 levels was negatively correlated with clinical PGD grades (Grade 2 PGD vs Grade 0 PGD: p = 0.042; Grade 3 PGD vs Grade 0 PGD: p = 0.004). Molecular analysis demonstrated that miR-21 targeted key components in the toll-like receptor (TLR) signaling pathway, including TLR4, IRAK3 and CXCL10. Further, incubation of THP-1 cells with cell-free BAL from severe PGD resulted in transactivation of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In contrast, increased expression of miR-21 resulted in marked suppression of IL-1-β and TNF-α production.
conclusionsUnderexpression of miR-21 may lead to the development of severe PGD by activating key components of the TLR pathway.
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