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. Metho...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; |
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| 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. |
| _version_ | 1878739560060420096 |
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| author | Marañon, Patricia |
| 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 |
| author_browse | Ampuero Herrojo, Javier Fernandez-Garcia, Carlos Ernesto Gallego Durán, Rocío Garcia-Monzon, Carmelo Gonzalez-Rodríguez, Agueda Isaza, Stephania C Marañon, Patricia Montero-Vallejo, Rocio Rey, Esther Romero Gómez, Manuel Valverde, Angela M de Cia, Javier Rodriguez |
| 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 |
| collection | idUS. Depósito de Investigación de la Universidad de Sevilla |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_c3d1a1a7fcf4e047feb4503bd47a8a67 |
| institution | Universidad de Sevilla (US) |
| instname_str | Universidad de Sevilla (US) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:idus.us.es:11441/183233 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | BMC (BioMed Central); BMC; Springer Science and Business Media |
| publisherStr | BMC (BioMed Central); BMC; Springer Science and Business Media |
| reponame_str | idUS. Depósito de Investigación de la Universidad de Sevilla |
| spelling | Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis 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 BMP8A Bone morphogenetic proteins Hepatic stellate cells Liver fibrosis Non-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 Media https://hdl.handle.net/11441/183233 https://doi.org/10.1186/s40364-023-00489-2 |
| 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. |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | BMP8A Bone morphogenetic proteins Hepatic stellate cells Liver fibrosis Non-invasive diagnosis. |
| topic_facet | BMP8A Bone morphogenetic proteins Hepatic stellate cells Liver fibrosis Non-invasive diagnosis. |
| url | https://hdl.handle.net/11441/183233 https://doi.org/10.1186/s40364-023-00489-2 |