Evidence map›Paper›PMID 35194091›Full record

ArticleScientific reports2022

Protein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis.

Davide Povero, Masahiko Tameda, Akiko Eguchi, Wenhua Ren, Jihoon Kim, Robert Myers, Zachary D Goodman, Stephen A Harrison, Arun J Sanyal, Jaime Bosch and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 13% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 9 institutions in 2 countries.

Davide Povero *Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Masahiko Tameda *Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, 3020 Children's Way, MC 5030, San Diego, CA, 92103-8450, USA.
Akiko EguchiDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, 3020 Children's Way, MC 5030, San Diego, CA, 92103-8450, USA.
Wenhua RenGenomics and Microarray Core, University of Colorado Denver, Aurora, CO, USA.
Jihoon KimDepartment of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
Robert MyersGilead Sciences, Inc., Foster City, CA, USA.
Zachary D GoodmanInova Fairfax Hospital, Falls Church, VA, USA.
Stephen A HarrisonPinnacle Clinical Research, San Antonio, TX, USA.
Arun J SanyalVirginia Commonwealth University, Richmond, VA, USA.
Jaime BoschDepartment of Visceral Surgery and Medicine and Department for Biomedical Research, Inselspital, University of Bern, Bern, Switzerland.
Lucila Ohno-MachadoDepartment of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
Ariel E FeldsteinDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, 3020 Children's Way, MC 5030, San Diego, CA, 92103-8450, USA. afeldstein@health.ucsd.edu.
University of California, San Diego · USRady Children's Hospital-San Diego · USGilead Sciences (United States) · USInova Fairfax Hospital · USMayo Clinic in Arizona · USPinnacle Clinical Research · USUniversity of Bern · CHUniversity of Colorado Denver · USVirginia Commonwealth University · US

Funding

Sterile inflammation and pyroptotic cell death in liver fibrosisR01DK113592 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ariel Feldstein, HAROLD M HOFFMAN · 2017 to 2026
$4.8M
Gain of function mutations in inflammasome related genes in human and experimental alcoholic liver diseaseR01AA024206 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDSTEIN, ARIEL · 2019 to 2021
$988k
Gain of function mutations in inflammasome related genes in human and experimental alcoholic liver diseaseU01AA024206 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDSTEIN, ARIEL · 2017 to 2018
$671k
NIAAA NIH HHS R01 AA024206NIAAA NIH HHS U01 AA024206NIDDK NIH HHS R01 DK113592
6 · The paper itself

Abstract

Primary sclerosing cholangitis (PSC) is an idiopathic and heterogenous cholestatic liver disease characterized by chronic inflammation and fibrosis of the biliary tree. Currently, no effective therapies are available for this condition, whose incidence is rising. At present, specificity and sensitivity of current serum markers used to diagnose PSC are limited and often unreliable. In this study, we characterize circulating extracellular vesicles and provide supporting data on their potential use as novel surrogate biomarkers for PSC. EVs are membrane surrounded structures, 100-1000 nm in size, released by cells under various conditions and which carry a variety of bioactive molecules, including small non-coding RNAs, lipids and proteins. In recent years, a large body of evidence has pointed to diagnostic implications of EVs and relative cargo in various human diseases. We isolated EVs from serum of well-characterized patients with PSC or control subjects by differential centrifugation and size-exclusion chromatography. A complete characterization identified elevated levels of circulating EVs in PSC patients compared to healthy control subjects (2000 vs. 500 Calcein-FITC + EVs/μL). Tissue and cell specificity of circulating EVs was assessed by identification of liver-specific markers and cholangiocyte marker CK-19. Further molecular characterization identified 282 proteins that were differentially regulated in PSC-derived compared to healthy control-EVs. Among those, IL-13Ra1 was the most significantly and differentially expressed protein in PSC-derived EVs and correlated with the degree of liver fibrosis. In addition to protein profiling, we performed a miRNA-sequencing analysis which identified 11 among established, liver-specific (e.g., miR-122 and miR-192) and novel miRNAs. One of the newly identified miRNAs, miR-4645-3p, was significantly up-regulated fourfold in PSC-derived EVs compared to circulating EVs isolated from healthy controls. This study provides supporting evidence of the potential role of circulating EVs and associated protein and miRNA cargo as surrogate noninvasive and reliable biomarker for PSC.

Indexed as

AdultAgedBiomarkersCholangitis, SclerosingExtracellular VesiclesFemaleGene ExpressionHumansInterleukin-13 Receptor alpha1 SubunitLiver CirrhosisMaleMicroRNAsMiddle AgedYoung AdultBiomarkersIL13RA1 protein, humanInterleukin-13 Receptor alpha1 SubunitMicroRNAs

Identifiers

PMID35194091
PMCPMC8863778
OpenAlexW4213096971

What OpenQuestion holds

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Registered trials

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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.