Evidence map›Paper›PMID 25979625›Full record

ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2015

MicroRNA-144 dysregulates the transforming growth factor-β signaling cascade and contributes to the development of bronchiolitis obliterans syndrome after human lung transplantation.

Zhongping Xu, Sabarinathan Ramachandran, Muthukumar Gunasekaran, Fangyu Zhou, Elbert Trulock, Daniel Kreisel, Ramsey Hachem, Thalachallour Mohanakumar

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03562416 (Nintedanib Plus Usual Transplant Care Compared to Usual Transplant Care Alone After Single Lung Transplantation in Patients With Idiopathic Pulmonary Fibrosis), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03562416 phase2terminatednot on this mapstarted 2019, after this paper: background citation

Nintedanib Plus Usual Transplant Care Compared to Usual Transplant Care Alone After Single Lung Transplantation in Patients With Idiopathic Pulmonary Fibrosis: a Pilot Randomized Controlled Trial

TypeinterventionalSponsorTemple UniversityRan2019 to 2021Enrolled1ConditionsIdiopathic Pulmonary Fibrosis, Lung Transplant, ComplicationsArmsNintedanib, Placebo Oral Tablet
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 45 citations in OpenAlex.

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  6. Restrictive allograft syndrome vs bronchiolitis obliterans syndrome: Immunological and molecular characterization of circulating exosomes.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
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  19. Significant role for microRNA-21 affecting toll-like receptor pathway in primary graft dysfunction after human lung transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2017
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  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Zhongping XuDepartments of Surgery.
Sabarinathan RamachandranDepartments of Surgery.
Muthukumar GunasekaranDepartments of Surgery.
Fangyu ZhouDepartments of Surgery.
Elbert TrulockMedicine.
Daniel KreiselDepartments of Surgery.
Ramsey HachemMedicine.
Thalachallour MohanakumarDepartments of Surgery; Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: kumart@wustl.edu.
Washington University in St. Louis · US

Funding

IMMUNE MECHANISMS OF REJECTION IN HUMAN LUNG ALLOGRAFTSR01HL056643 · NHLBI · WASHINGTON UNIVERSITY · PI MOHANAKUMAR, THALACHALLOUR · 1996 to 2015
$6.5M
NHLBI NIH HHS R01 HL056643NHLBI NIH HHS R01-HL0-56643-13
6 · The paper itself

Abstract

backgroundBronchiolitis obliterans syndrome (BOS), chronic lung allograft rejection, remains an impediment for the function of the transplanted organ. In this study, we defined the role of the microRNA (miRNA) miR-144 in fibroproliferation leading to BOS.

methodsBiopsy specimens were obtained from 20 lung transplant recipients with BOS((+)) and 19 without BOS((-)). Expression of miR-144 and its target, transforming growth factor-β (TGF-β)-induced factor homeobox 1(TGIF1), were analyzed by real-time polymerase chain reaction and Western blot. Overexpression of miR-144 and luciferase reporter genes were performed to elucidate miRNA-target interactions. The function of miR-144 was evaluated by transfecting fibroblasts and determining the response to TGF-β by analyzing Sma- and Mad-related family (Smads), fibroblast growth factor, TGF-β, and vascular endothelial growth factor. Smooth muscle actin-α-positive stress fibers and F-actin filaments in lung fibroblasts were analyzed by immunofluorescence.

resultsAnalysis of miR-144 in the biopsy specimens demonstrated 4.1 ± 0.8-fold increases in BOS(+) compared with BOS(-) patients, with a significant reduction in TGIF1 (3.6 ± 1.2-fold), a corepressor of Smads. In vitro transfection confirmed that over-expression of miR-144 results in a reduction in TGIF1 and an increase in SMAD2, SMAD4, fibroblast growth factor-6, TGF-β, and vascular endothelial growth factor. Increasing miR-144 by transfecting, increased smooth muscle actin-α and fibronectin, and knockdown of miR-144 diminished fibrogenesis in MRC-5 fibroblasts.

conclusionsmiR-144 is a critical regulator of the TGF-β signaling cascade and is over-expressed in lungs with BOS. Therefore, miR-144 is a potential target toward preventing fibrosis leading to BOS after lung transplant.

Indexed as

Lung TransplantationBlotting, WesternBronchiolitis ObliteransFemaleFibroblast Growth FactorsFibroblastsFibrosisFluorescent Antibody TechniqueHomeodomain ProteinsHumansLungMaleMicroRNAsMiddle AgedMusclesReal-Time Polymerase Chain ReactionFibroblast Growth FactorsHomeodomain ProteinsMicroRNAsMIRN144 microRNA, humanRepressor ProteinsSmad2 ProteinSmad4 ProteinSmad ProteinsTGIF1 protein, humanTransforming Growth Factor betaVascular Endothelial Growth Factor Abronchiolitis obliterans syndromelung transplantationmicroRNATGF-β.

Identifiers

PMID25979625
PMCPMC4536097
OpenAlexW2143760046

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.