Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients
Abstract Background Acute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and...
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BMC
2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06100-6 |
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| author | Liu Yang Zhuo Xu Zhenyan Wang Fangping Ding Zhipeng Wu Xiaoqian Shi Jing Wang Yingmin Ma Jiawei Jin |
| author_facet | Liu Yang Zhuo Xu Zhenyan Wang Fangping Ding Zhipeng Wu Xiaoqian Shi Jing Wang Yingmin Ma Jiawei Jin |
| author_sort | Liu Yang |
| collection | DOAJ |
| description | Abstract Background Acute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and its adverse transition to pro-inflammation has an important role in the pathogenesis of ARDS. However, the relationship between HDL protein constituents and functional remodeling is unknown in ARDS. Methods Proteomic techniques were applied to examine the protein profile changes in HDL from septic-ARDS patients versus HDL from healthy controls across two distinct cohorts: a discovery cohort (8 patients and 8 healthy controls) and a validation cohort (22 patients and 10 healthy controls). The changed components significantly associated with prognosis were identified. Luminex assessed the levels of 38 plasma cytokines and chemokines. The in vitro constructed pro-SFTPB enriched HDL was applied to confirm the effect on M1 polarization of THP1-derived macrophage. Results 18 proteins were validated from 102 changed HDL proteins identified in the discovery cohort, including HDL particle components, such as apolipoproteins, pro-inflammatory substances known as serum amyloid As (SAAs), and anti-oxidative proteins like paraoxonases (PONs). Among these proteins, only the increase of pro-SFTPB in HDL was significantly associated with poor prognosis of ARDS patients. Notably, HDL-pro-SFTPB level was correlated with plasma pro-inflammatory cytokines and chemokines levels. The correlation assay of pro-SFTPB with other HDL components showed that it was positively and negatively correlated with SAA2 and PON3, respectively. Furthermore, the in vitro studies confirmed that the pro-SFTPB enriched HDL significantly promoted M1 polarization of monocyte-derived macrophages. Conclusions The increase of HDL-pro-SFTPB promotes HDL pro-inflammatory transition during septic ARDS, leading to exacerbated progression of ARDS through enhancing M1 macrophage polarization. HDL-pro-SFTPB could be a useful prognostic biomarker for septic ARDS. |
| format | Article |
| id | doaj-art-fbb1b3d1552a4339a06c5e022a96a9a8 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-fbb1b3d1552a4339a06c5e022a96a9a82025-01-19T12:37:21ZengBMCJournal of Translational Medicine1479-58762025-01-0123111710.1186/s12967-025-06100-6Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patientsLiu Yang0Zhuo Xu1Zhenyan Wang2Fangping Ding3Zhipeng Wu4Xiaoqian Shi5Jing Wang6Yingmin Ma7Jiawei Jin8Department of Respiratory and Critical Care Medicine, Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical UniversityAbstract Background Acute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and its adverse transition to pro-inflammation has an important role in the pathogenesis of ARDS. However, the relationship between HDL protein constituents and functional remodeling is unknown in ARDS. Methods Proteomic techniques were applied to examine the protein profile changes in HDL from septic-ARDS patients versus HDL from healthy controls across two distinct cohorts: a discovery cohort (8 patients and 8 healthy controls) and a validation cohort (22 patients and 10 healthy controls). The changed components significantly associated with prognosis were identified. Luminex assessed the levels of 38 plasma cytokines and chemokines. The in vitro constructed pro-SFTPB enriched HDL was applied to confirm the effect on M1 polarization of THP1-derived macrophage. Results 18 proteins were validated from 102 changed HDL proteins identified in the discovery cohort, including HDL particle components, such as apolipoproteins, pro-inflammatory substances known as serum amyloid As (SAAs), and anti-oxidative proteins like paraoxonases (PONs). Among these proteins, only the increase of pro-SFTPB in HDL was significantly associated with poor prognosis of ARDS patients. Notably, HDL-pro-SFTPB level was correlated with plasma pro-inflammatory cytokines and chemokines levels. The correlation assay of pro-SFTPB with other HDL components showed that it was positively and negatively correlated with SAA2 and PON3, respectively. Furthermore, the in vitro studies confirmed that the pro-SFTPB enriched HDL significantly promoted M1 polarization of monocyte-derived macrophages. Conclusions The increase of HDL-pro-SFTPB promotes HDL pro-inflammatory transition during septic ARDS, leading to exacerbated progression of ARDS through enhancing M1 macrophage polarization. HDL-pro-SFTPB could be a useful prognostic biomarker for septic ARDS.https://doi.org/10.1186/s12967-025-06100-6ARDSSepsisPro-SFTPBHDL proteomicsMacrophage |
| spellingShingle | Liu Yang Zhuo Xu Zhenyan Wang Fangping Ding Zhipeng Wu Xiaoqian Shi Jing Wang Yingmin Ma Jiawei Jin Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients Journal of Translational Medicine ARDS Sepsis Pro-SFTPB HDL proteomics Macrophage |
| title | Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients |
| title_full | Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients |
| title_fullStr | Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients |
| title_full_unstemmed | Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients |
| title_short | Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients |
| title_sort | increased pro sftpb in hdl promotes the pro inflammatory transition of hdl and represents a sign of poor prognosis in ards patients |
| topic | ARDS Sepsis Pro-SFTPB HDL proteomics Macrophage |
| url | https://doi.org/10.1186/s12967-025-06100-6 |
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