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

Biomarker Research

Research

Águeda González-Rodríguez¹  Ángela M. Valverde¹  Stephania C. Isaza²  Patricia Marañón²  Carlos Ernesto Fernández-García²  Esther Rey²  Javier Rodríguez de Cía²  Carmelo García-Monzón³  Rocío Montero-Vallejo⁴  Manuel Romero-Gómez⁴  Rocío Gallego-Durán⁴  Javier Ampuero⁴ 

[1] Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM), Madrid, Spain;Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM), Madrid, Spain;Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spain;Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spain;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain;SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío, Seville, Spain;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain;

关键词: Liver fibrosis;    Bone morphogenetic proteins;    BMP8A;    Non-invasive diagnosis;    Hepatic stellate cells;   

DOI  :  10.1186/s40364-023-00489-2

 received in 2023-01-03, accepted in 2023-04-18,  发布年份 2023

来源: Springer

【 摘 要 】

Background & AimsAdvanced 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.MethodsHistological 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).ResultsBmp8a 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.ConclusionThis 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.

【 授权许可】

CC BY   
© Yumed Inc. and BioMed Central Ltd., part of Springer Nature 2023

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