Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis

Background & aims: Advanced hepatic fibrosis is the main risk factor of liver-related morbidity and mortality in patients with chronic liver disease. In this study, we assessed the potential role of bone morphogenetic protein 8A (BMP8A) as a novel target involved in liver fibrosis progression. M...

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Authors: Marañon, Patricia, Isaza, Stephania C, Fernandez-Garcia, Carlos Ernesto, Rey, Esther, Gallego Durán, Rocío, Montero-Vallejo, Rocio, de Cia, Javier Rodriguez, Ampuero Herrojo, Javier, Valverde, Angela M, Romero Gómez, Manuel, Garcia-Monzon, Carmelo, Gonzalez-Rodríguez, Agueda
Format: article
Status:Published version
Publication Date:2023
Country:España
Institution:Universidad de Sevilla (US)
Repository:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/183233
Online Access:https://hdl.handle.net/11441/183233
https://doi.org/10.1186/s40364-023-00489-2
Access Level:Open access
Keyword:BMP8A
Bone morphogenetic proteins
Hepatic stellate cells
Liver fibrosis
Non-invasive diagnosis.
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repository_id_str
spelling Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosisMarañon, PatriciaIsaza, Stephania CFernandez-Garcia, Carlos ErnestoRey, EstherGallego Durán, RocíoMontero-Vallejo, Rociode Cia, Javier RodriguezAmpuero Herrojo, JavierValverde, Angela MRomero Gómez, ManuelGarcia-Monzon, CarmeloGonzalez-Rodríguez, AguedaBMP8ABone morphogenetic proteinsHepatic stellate cellsLiver fibrosisNon-invasive diagnosis.Background & aims: Advanced hepatic fibrosis is the main risk factor of liver-related morbidity and mortality in patients with chronic liver disease. In this study, we assessed the potential role of bone morphogenetic protein 8A (BMP8A) as a novel target involved in liver fibrosis progression. Methods: Histological assessment and BMP8A expression were determined in different murine models of hepatic fibrosis. Furthermore, serum BMP8A was measured in mice with bile duct ligation (BDL), in 36 subjects with histologically normal liver (NL) and in 85 patients with biopsy-proven non-alcoholic steatohepatitis (NASH): 52 with non- or mild fibrosis (F0-F2) and 33 with advanced fibrosis (F3-F4). BMP8A expression and secretion was also determined in cultured human hepatocyte-derived (Huh7) and human hepatic stellate (LX2) cells stimulated with transforming growth factor ꞵ (TGFꞵ). Results: Bmp8a mRNA levels were significantly upregulated in livers from fibrotic mice compared to control animals. Notably, serum BMP8A levels were also elevated in BDL mice. In addition, in vitro experiments showed increased expression and secretion to the culture supernatant of BMP8A in both Huh7 and LX2 cells treated with TGFꞵ. Noteworthy, we found that serum BMP8A levels were significantly higher in NASH patients with advanced fibrosis than in those with non- or mild fibrosis. In fact, the AUROC of circulating BMP8A concentrations to identify patients with advanced fibrosis (F3-F4) was 0.74 (p˂0.0001). Moreover, we developed an algorithm based on serum BMP8A levels that showed an AUROC of 0.818 (p˂0.0001) to predict advanced fibrosis in NASH patients. Conclusion: This study provides experimental and clinical evidence indicating that BMP8A is a novel molecular target linked to liver fibrosis and introduces an efficient algorithm based on serum BMP8A levels to screen patients at risk for advanced hepatic fibrosis.BMC (BioMed Central); BMC; Springer Science and Business MediaMedicinaCTS1106: Enfermedades Hepáticas y DigestivasGilead SciencesInstituto de Salud Carlos III2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/183233https://doi.org/10.1186/s40364-023-00489-2reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBiomarker Research, 11 (1), 46.GLD18/00151CD20/00199PI16/00853https://link.springer.com/article/10.1186/s40364-023-00489-2info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1832332026-06-17T12:51:07Z
dc.title.none.fl_str_mv Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
title Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
spellingShingle Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
Marañon, Patricia
BMP8A
Bone morphogenetic proteins
Hepatic stellate cells
Liver fibrosis
Non-invasive diagnosis.
title_short Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
title_full Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
title_fullStr Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
title_full_unstemmed Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
title_sort Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
dc.creator.none.fl_str_mv Marañon, Patricia
Isaza, Stephania C
Fernandez-Garcia, Carlos Ernesto
Rey, Esther
Gallego Durán, Rocío
Montero-Vallejo, Rocio
de Cia, Javier Rodriguez
Ampuero Herrojo, Javier
Valverde, Angela M
Romero Gómez, Manuel
Garcia-Monzon, Carmelo
Gonzalez-Rodríguez, Agueda
author Marañon, Patricia
author_facet Marañon, Patricia
Isaza, Stephania C
Fernandez-Garcia, Carlos Ernesto
Rey, Esther
Gallego Durán, Rocío
Montero-Vallejo, Rocio
de Cia, Javier Rodriguez
Ampuero Herrojo, Javier
Valverde, Angela M
Romero Gómez, Manuel
Garcia-Monzon, Carmelo
Gonzalez-Rodríguez, Agueda
author_role author
author2 Isaza, Stephania C
Fernandez-Garcia, Carlos Ernesto
Rey, Esther
Gallego Durán, Rocío
Montero-Vallejo, Rocio
de Cia, Javier Rodriguez
Ampuero Herrojo, Javier
Valverde, Angela M
Romero Gómez, Manuel
Garcia-Monzon, Carmelo
Gonzalez-Rodríguez, Agueda
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
CTS1106: Enfermedades Hepáticas y Digestivas
Gilead Sciences
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv BMP8A
Bone morphogenetic proteins
Hepatic stellate cells
Liver fibrosis
Non-invasive diagnosis.
topic BMP8A
Bone morphogenetic proteins
Hepatic stellate cells
Liver fibrosis
Non-invasive diagnosis.
description Background & aims: Advanced hepatic fibrosis is the main risk factor of liver-related morbidity and mortality in patients with chronic liver disease. In this study, we assessed the potential role of bone morphogenetic protein 8A (BMP8A) as a novel target involved in liver fibrosis progression. Methods: Histological assessment and BMP8A expression were determined in different murine models of hepatic fibrosis. Furthermore, serum BMP8A was measured in mice with bile duct ligation (BDL), in 36 subjects with histologically normal liver (NL) and in 85 patients with biopsy-proven non-alcoholic steatohepatitis (NASH): 52 with non- or mild fibrosis (F0-F2) and 33 with advanced fibrosis (F3-F4). BMP8A expression and secretion was also determined in cultured human hepatocyte-derived (Huh7) and human hepatic stellate (LX2) cells stimulated with transforming growth factor ꞵ (TGFꞵ). Results: Bmp8a mRNA levels were significantly upregulated in livers from fibrotic mice compared to control animals. Notably, serum BMP8A levels were also elevated in BDL mice. In addition, in vitro experiments showed increased expression and secretion to the culture supernatant of BMP8A in both Huh7 and LX2 cells treated with TGFꞵ. Noteworthy, we found that serum BMP8A levels were significantly higher in NASH patients with advanced fibrosis than in those with non- or mild fibrosis. In fact, the AUROC of circulating BMP8A concentrations to identify patients with advanced fibrosis (F3-F4) was 0.74 (p˂0.0001). Moreover, we developed an algorithm based on serum BMP8A levels that showed an AUROC of 0.818 (p˂0.0001) to predict advanced fibrosis in NASH patients. Conclusion: This study provides experimental and clinical evidence indicating that BMP8A is a novel molecular target linked to liver fibrosis and introduces an efficient algorithm based on serum BMP8A levels to screen patients at risk for advanced hepatic fibrosis.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/183233
https://doi.org/10.1186/s40364-023-00489-2
url https://hdl.handle.net/11441/183233
https://doi.org/10.1186/s40364-023-00489-2
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biomarker Research, 11 (1), 46.
GLD18/00151
CD20/00199
PI16/00853
https://link.springer.com/article/10.1186/s40364-023-00489-2
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BMC (BioMed Central); BMC; Springer Science and Business Media
publisher.none.fl_str_mv BMC (BioMed Central); BMC; Springer Science and Business Media
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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