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Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

George Papatheodoridis; Katherine Johnson; Yasaman Vali; Pierre Chaumat; David Wenn; James Clark; Paul Hockings; Antonio Vidal-Puig; Fiona Oakley; Lori Jennings; Christian Rosenquist; Michael Kalutkiewicz; Richard Ehman; Joel Myers; Stefan Neubauer; Jenny Lee; Carla Yunis; Clifford Brass; Daniel Rasmussen; Aldo Trylesinski; Judith Ertle; Saskia van Mil; Salvatore Petta; Óscar Millet; Karine Clément; Raluca Pais; Hannele Yki-Järvinen; Antonia Sinisi; Morten Karsdal; Michele Vacca; Mette Juul Fisker; Matt Kelly; Chiara Rosso; Lynda Doward; Matthew J Barter; Luca Valenti; Diana Leeming; Mette Skalshøi Kjær; Jean-Francois Dufour; Vlad Ratziu; Rachel Queen; Fabio Marra; Heather J Cordell; Patrick M Bossuyt; on behalf of the LITMUS Consortium Investigators; Sarah H Charlton; Simon J Cockell; Rajarshi Banerjee; Jörn M Schattenberg; Matej Orešič; Jeremy F Cobbold; Karine Clement; Ann K Daly; James Twiss; Hadi Zafarmand; Quentin M Anstee; Kristy Wonders; Christopher P Day; Luca Miele; Jerome Boursier; M Julia Brosnan; Lars Friis Mikkelsen; Dina Tiniakos; Gideon Ho; Peter J Leary; Guruprasad P Aithal; Maria Manuela Tonini; Isabel Fernández; Rob Myers; Per Qvist; Kay Pepin; Stergios Kechagias; Henrik Landgren; Sudha Shankar; Rebecca Darlay; Sven Francque; Michael Allison; Rocío Gallego-Durán; Phil Newsome; Pierre Bedossa; Jeremy Palmer; Jose Mato; Cecília Maria Pereira Rodrigues; Aidan McGlinchey; Elisabeth Erhardtsen; Elisabetta Bugianesi; Melissa Miller; Michael Pavlides; Detlef Schuppan; Tuulia Hyötyläinen; Manuel Romero-Gomez; Charlotte Erpicum; Miljen Martic; Michalina Zatorska; Kevin Duffin; Stephen Harrison; Yang-Lin Liu; Diane Shevell; Olivier Govaere; Richard Torstenson; Partho Sen; Maria-Magdalena Balp; Ferenc Mozes; Rachel Ostroff; Mattias Ekstedt; Pablo Ortiz; Salma Akhtar; Estelle Sandt; Theresa Tuthill; Helena Cortez-Pinto; Amalia Gastaldelli; Céline Fournier; Tim Hardy; Christian Trautwein; Diane Whalley; Vanessa Pellegrinelli; Kimmo Porthan; Adriaan G Holleboom; Andreas Geier; Ramy Younes; Leigh Alexander; Elizabeth Shumbayawonda; Rémy Hanf; Maurizio Parola; Andrea Dennis; Guido Hanauer; Sergio Rodriguez Cuenca

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

George Papatheodoridis
Katherine Johnson
Yasaman Vali
Pierre Chaumat
David Wenn
James Clark
Paul Hockings
Antonio Vidal-Puig
Fiona Oakley
Lori Jennings
Christian Rosenquist
Michael Kalutkiewicz
Richard Ehman
Joel Myers
Stefan Neubauer
Jenny Lee
Carla Yunis
Clifford Brass
Daniel Rasmussen
Aldo Trylesinski
Judith Ertle
Saskia van Mil
Salvatore Petta
Óscar Millet
Karine Clément
Raluca Pais
Hannele Yki-Järvinen
Antonia Sinisi
Morten Karsdal
Michele Vacca
Mette Juul Fisker
Matt Kelly
Chiara Rosso
Lynda Doward
Matthew J Barter
Luca Valenti
Diana Leeming
Mette Skalshøi Kjær
Jean-Francois Dufour
Vlad Ratziu
Rachel Queen
Fabio Marra
Heather J Cordell
Patrick M Bossuyt
on behalf of the LITMUS Consortium Investigators
Sarah H Charlton
Simon J Cockell
Rajarshi Banerjee
Jörn M Schattenberg
Matej Orešič
Jeremy F Cobbold
Karine Clement
Ann K Daly
James Twiss
Hadi Zafarmand
Quentin M Anstee
Kristy Wonders
Christopher P Day
Luca Miele
Jerome Boursier
M Julia Brosnan
Lars Friis Mikkelsen
Dina Tiniakos
Gideon Ho
Peter J Leary
Guruprasad P Aithal
Maria Manuela Tonini
Isabel Fernández
Rob Myers
Per Qvist
Kay Pepin
Stergios Kechagias
Henrik Landgren
Sudha Shankar
Rebecca Darlay
Sven Francque
Michael Allison
Rocío Gallego-Durán
Phil Newsome
Pierre Bedossa
Jeremy Palmer
Jose Mato
Cecília Maria Pereira Rodrigues
Aidan McGlinchey
Elisabeth Erhardtsen
Elisabetta Bugianesi
Melissa Miller
Michael Pavlides
Detlef Schuppan
Tuulia Hyötyläinen
Manuel Romero-Gomez
Charlotte Erpicum
Miljen Martic
Michalina Zatorska
Kevin Duffin
Stephen Harrison
Yang-Lin Liu
Diane Shevell
Olivier Govaere
Richard Torstenson
Partho Sen
Maria-Magdalena Balp
Ferenc Mozes
Rachel Ostroff
Mattias Ekstedt
Pablo Ortiz
Salma Akhtar
Estelle Sandt
Theresa Tuthill
Helena Cortez-Pinto
Amalia Gastaldelli
Céline Fournier
Tim Hardy
Christian Trautwein
Diane Whalley
Vanessa Pellegrinelli
Kimmo Porthan
Adriaan G Holleboom
Andreas Geier
Ramy Younes
Leigh Alexander
Elizabeth Shumbayawonda
Rémy Hanf
Maurizio Parola
Andrea Dennis
Guido Hanauer
Sergio Rodriguez Cuenca
Katso/Avaa
1-s2.0-S2589555921001853-main.pdf (523.8Kb)
Lataukset: 

Elsevier
doi:10.1016/j.jhepr.2021.100409
URI
https://www.sciencedirect.com/science/article/pii/S2589555921001853
Näytä kaikki kuvailutiedot
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe202301142845
Tiivistelmä

Background & Aims
Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.

Methods
We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR.

Results
Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p.

Conclusions
Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD.

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