H3K4me3‐Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti‐β2GPI‐Treated Monocytes
Abstract: Antiphospholipid syndrome (APS) is characterized by thrombus formation, poor pregnancy outcomes, and a proinflammatory response. H3K4me3‐related monocytes activation are key regulators of APS pathogenesis. Therefore, H3K4me3 CUT&Tag and ATAC‐seq are performed to examine the epigenetic profiles. The results indicate that the H3K4me3 signal and chromatin accessibility at the FOXJ2 promoter are enhanced in an in vitro monocyte model by stimulation with β2GPI/anti‐β2GPI, which mimics APS, and decreases after OICR‐9429 administration. Furthermore, FOXJ2 is highly expressed in patients with primary APS (PAPS) and is the highest in patients with triple‐positive antiphospholipid antibodies (aPLs). Mechanistically, FOXJ2 directly binds to the SLAMF8 promoter and activates SLAMF8 transcription. SLAMF8 further interacts with TREM1 to stimulate TLR4/NF‐κB signaling and prohibit autophagy. Knockdown of FOXJ2, SLAMF8, or TREM1 blocks TLR4/NF‐κB and provokes autophagy, subsequently inhibiting the release of inflammatory and thrombotic indicators. A mouse model of vascular APS is established via β2GPI intraperitoneal injection, and the results suggest that OICR‐9429 administration attenuates the inflammatory response and thrombus formation by inactivating FOXJ2/SLAMF8/TREM1 signaling. These findings highlight the overexpression of H3K4me3‐mediated FOXJ2 in APS, which consequently accelerates APS pathogenesis by triggering inflammation and thrombosis via boosting the SLAMF8/TREM1 axis. Therefore, OICR‐9429 is a promising candidate drug for APS therapy.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
H3K4me3‐Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti‐β2GPI‐Treated Monocytes ; day:19 ; month:04 ; year:2024 ; extent:16
Advanced science ; (19.04.2024) (gesamt 16)
- Creator
-
Tan, Yuan
Qiao, Jiao
Yang, Shuo
Liu, Hongchao
Wang, Qingchen
Liu, Qi
Feng, Weimin
Cui, Liyan
- DOI
-
10.1002/advs.202309140
- URN
-
urn:nbn:de:101:1-2404191437459.033418845622
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:56 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Tan, Yuan
- Qiao, Jiao
- Yang, Shuo
- Liu, Hongchao
- Wang, Qingchen
- Liu, Qi
- Feng, Weimin
- Cui, Liyan
Other Objects (12)
An Artificial Intelligence‐Based Motion Trajectory Prediction of Fibrous Matters
Acousto-optic stimuli to promote coherent 40-Hz frequency entrainment effect
Analysis and improvement of human-induced vibration comfort of articulated steel pedestrian bridges
Author Correction: Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer
Quantum state tomography with locally purified density operators and local measurements
Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer
Bilingual education in China: a qualitative synthesis of research on models and perceptions
Crystal structure of 1′,3′-dihydro-2,2′-spirobi (indene)-1,3-dione, C 17 H 12 O 2
A truncated nuclear norm and graph-Laplacian regularized low-rank representation method for tumor clustering and gene selection
Serum exosomal microRNA-1258 may as a novel biomarker for the diagnosis of acute exacerbations of chronic obstructive pulmonary disease
Incidence and risk factors of admission deep venous thrombosis in nonagenarians and centenarians with intertrochanteric fracture: a retrospective study
Extracellular vesicles mediated gastric cancer immune response: tumor cell death or immune escape?
An Artificial Intelligence‐Based Motion Trajectory Prediction of Fibrous Matters
Acousto-optic stimuli to promote coherent 40-Hz frequency entrainment effect
Analysis and improvement of human-induced vibration comfort of articulated steel pedestrian bridges
Author Correction: Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer
Quantum state tomography with locally purified density operators and local measurements
Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer
Bilingual education in China: a qualitative synthesis of research on models and perceptions
Crystal structure of 1′,3′-dihydro-2,2′-spirobi (indene)-1,3-dione, C 17 H 12 O 2
A truncated nuclear norm and graph-Laplacian regularized low-rank representation method for tumor clustering and gene selection
Serum exosomal microRNA-1258 may as a novel biomarker for the diagnosis of acute exacerbations of chronic obstructive pulmonary disease
Incidence and risk factors of admission deep venous thrombosis in nonagenarians and centenarians with intertrochanteric fracture: a retrospective study
Extracellular vesicles mediated gastric cancer immune response: tumor cell death or immune escape?
An Artificial Intelligence‐Based Motion Trajectory Prediction of Fibrous Matters
Acousto-optic stimuli to promote coherent 40-Hz frequency entrainment effect
Analysis and improvement of human-induced vibration comfort of articulated steel pedestrian bridges
Author Correction: Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer
Quantum state tomography with locally purified density operators and local measurements
Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer
Bilingual education in China: a qualitative synthesis of research on models and perceptions
Crystal structure of 1′,3′-dihydro-2,2′-spirobi (indene)-1,3-dione, C 17 H 12 O 2
A truncated nuclear norm and graph-Laplacian regularized low-rank representation method for tumor clustering and gene selection
Serum exosomal microRNA-1258 may as a novel biomarker for the diagnosis of acute exacerbations of chronic obstructive pulmonary disease
Incidence and risk factors of admission deep venous thrombosis in nonagenarians and centenarians with intertrochanteric fracture: a retrospective study