N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction

2021 ◽  
Author(s):  
Mudassir M. Banday ◽  
Archit Kumar ◽  
Grant Vestal ◽  
Jaskaran Sethi ◽  
Kapil N. Patel ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction

scholarly journals MiR-21 in Lung Transplant Recipients With Chronic Lung Allograft Dysfunction

2022 ◽  
Vol 35 ◽  
Author(s):  
Naofumi Miyahara ◽  
Alberto Benazzo ◽  
Felicitas Oberndorfer ◽  
Akinori Iwasaki ◽  
Viktoria Laszlo ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Bronchiolitis Obliterans Syndrome ◽  
Micro Rna ◽  
Serum Samples ◽  
Mesenchymal Transition ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Notch Intracellular Domain ◽  
Restrictive Allograft Syndrome ◽  
Lung Transplant Recipients

Background: Micro-RNA-21 (miR-21) is a post-translational regulator involved in epithelial-to-mesenchymal transition (EMT). Since EMT is thought to contribute to chronic lung allograft dysfunction (CLAD), we aimed to characterize miR-21 expression and distinct EMT markers in CLAD.Methods: Expression of miR-21, vimentin, Notch intracellular domain (NICD) and SMAD 2/3 was investigated in explanted CLAD lungs of patients who underwent retransplantation. Circulating miR-21 was determined in collected serum samples of CLAD and matched stable recipients.Results: The frequency of miR-21 expression was higher in restrictive allograft syndrome (RAS) than in bronchiolitis obliterans syndrome (BOS) specimens (86 vs 30%, p = 0.01); Vimentin, NICD and p-SMAD 2/3 were positive in 17 (100%), 12 (71%), and 7 (42%) BOS patients and in 7 (100%), 4 (57%) and 4 (57%) RAS cases, respectively. All four markers were negative in control tissue from donor lungs. RAS patients showed a significant increase in serum concentration of miR-21 over time as compared to stable recipients (p = 0.040).Conclusion: To the best of our knowledge this is the first study highlighting the role miR-21 in CLAD. Further studies are necessary to investigate the involvement of miR-21 in the pathogenesis of CLAD and its potential as a therapeutic target.

Epithelial-mesenchymal transition in chronic lung allograft dysfunction. Role of leucocyte microparticles

2016 ◽  
Author(s):  
Benjamin Renaud-Picard ◽  
Justine Toussaint ◽  
Fatiha El Ghazouani ◽  
Florence Toti ◽  
Laurence Kessler ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction

scholarly journals Cyclophilin A/CD147 Induces the Epithelial-to-mesenchymal Transition and Renal Fibrosis in Chronic Allograft Dysfunction by Regulating MAPK Signaling

2021 ◽  
Author(s):  
Xuzhong Liu ◽  
Zhiwang Tang ◽  
Xi Jiang ◽  
Tianwei Wang ◽  
Lun Zhao ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Epithelial To Mesenchymal Transition ◽  
Renal Allograft ◽  
Cyclophilin A ◽  
Mapk Signaling ◽  
Chronic Allograft Dysfunction ◽  
Mesenchymal Transition ◽  
Allograft Dysfunction

Abstract Objectives: Our study was designed to explore the role of Cyclophilin A (CyPA)/CD147 interactions in renal allograft fibrosis and chronic allograft dysfunction (CAD). Methods and materials: A rat renal transplant model with significant CAD was successfully identified. Renal allograft tissues and blood samples were collected. HE, Masson and immunohistochemistry staining were performed. Then human HK-2 cells were intervened by certain concentrations of CyPA, and total protein and mRNA were extracted. Western blot assay and PCR were performed to explore the protein and mRNA expression of CyPA, CD147 and epithelial-to-mesenchymal transition (EMT)-related biomarkers. CD147 siRNA and specific inhibitor of MAPK were used to explore the involved cellular mechanism.Results: We have successfully established and identified a 20-weeks renal transplant CAD model. We observed significant distributed and expressed CyPA and CD147 in the renal allograft fibrosis tissues. We also found the significant expression of CD147 and EMT-related markers in the HK-2 cells stimulated by CyPA. The CD147 siRNA confirmed the previous results in vitro. The selective inhibition of MAPK suggested the notable role of MAPK signaling pathway in the CyP/CD147 interactions involved in renal allograft fibrosis.Conclusions: Our study reported the positive relationship of CyPA/CD147 interactions with the renal allograft dysfunction. In vitro study suggested that CyPA could bind to CD147 and then induce the development of EMT process by MAPK signaling, thus contributing to the renal allograft fibrosis and CAD.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

Lung volumes predict survival in patients with chronic lung allograft dysfunction

Pneumologie ◽  
2017 ◽  
Vol 71 (S 01) ◽  
pp. S1-S125
Author(s):  
N Kneidinger ◽  
K Milger ◽  
S Janitza ◽  
F Ceelen ◽  
G Leuschner ◽  
...  
Keyword(s):  
Lung Volumes ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction
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