GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia
Abstract Background Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and proteinuria. PE poses a substantial threat to the health of both mothers and fetuses, and currently, there is no definitive treatment available. Recent studies have indicated that the transcrip...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-024-02229-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544869617598464 |
|---|---|
| author | Wushan Li Fei Hou Di Cheng Fengchun Gao Jin Wang Baoxia Cui |
| author_facet | Wushan Li Fei Hou Di Cheng Fengchun Gao Jin Wang Baoxia Cui |
| author_sort | Wushan Li |
| collection | DOAJ |
| description | Abstract Background Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and proteinuria. PE poses a substantial threat to the health of both mothers and fetuses, and currently, there is no definitive treatment available. Recent studies have indicated that the transcription factor GATA1 may be implicated in the pathological processes of PE, but the underlying mechanism remains elusive. NTRK2/cGMP–PKG signaling pathway plays a crucial role in regulating the function and polarization of macrophages, which are key immune cells at the maternal–fetal interface. This study aims to investigate the role of GATA1 in the pathogenesis of PE, with a specific focus on how GATA1-regulated TrkB/cGMP–PKG signaling in macrophages and its dysregulation contribute to the development of preeclampsia. Methods By employing THP-1 cells, co-culture systems of THP-1 cells and HTR-8/Svneo, HPVECs and Sprague–Dawley (SD) rats, in conjunction with gene knockdown and overexpression techniques, we explored the effects of GATA1 on the TrkB/cGMP–PKG signaling pathway. Transcriptomic sequencing, bioinformatics analysis, animal experiments, and clinical sample collection were conducted to validate the role of GATA1 in PE. Results Knockdown of GATA1 mitigated the symptoms of PE, and this effect was reversed by overexpression of TrkB. In comparison with the control group, the proportion of M2 cells elevated significantly in the sh-GATA1 group (P < 0.001). In addition, the protein expressions levels of TrkB, cGMP, and PKG were significantly decreased in the sh-GATA1 group were significantly decreased compared with those in the control group (P < 0.001, P < 0.001, P < 0.001, P < 0.05, respectively). Moreover, knockdown of GATA1 significantly promoted the migration rate and blood vessel formation of HTR-8/Svneo cells (P < 0.001, P < 0.05, respectively) which inhibited by overexpression of NTRK2 (P < 0.05, P < 0.01, respectively). Conclusions The study demonstrated that knockdown of GATA1 modulates M2 polarization of macrophage through the TrkB/cGMP–PKG signaling pathway, influencing the progression of PE. In addition, significant associations between GATA1 and the TrkB/cGMP–PKG signaling pathway were identified in the transcriptomic data from PE patient placentas. |
| format | Article |
| id | doaj-art-06ace521d05b4e76a73108b8cf69fe08 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-06ace521d05b4e76a73108b8cf69fe082025-01-12T12:12:47ZengBMCEuropean Journal of Medical Research2047-783X2025-01-0130111610.1186/s40001-024-02229-0GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsiaWushan Li0Fei Hou1Di Cheng2Fengchun Gao3Jin Wang4Baoxia Cui5Department of Obstetrics and Gynecology, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical UniversityDepartment of Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical UniversityDepartment of Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical UniversityDepartment of Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong UniversityAbstract Background Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and proteinuria. PE poses a substantial threat to the health of both mothers and fetuses, and currently, there is no definitive treatment available. Recent studies have indicated that the transcription factor GATA1 may be implicated in the pathological processes of PE, but the underlying mechanism remains elusive. NTRK2/cGMP–PKG signaling pathway plays a crucial role in regulating the function and polarization of macrophages, which are key immune cells at the maternal–fetal interface. This study aims to investigate the role of GATA1 in the pathogenesis of PE, with a specific focus on how GATA1-regulated TrkB/cGMP–PKG signaling in macrophages and its dysregulation contribute to the development of preeclampsia. Methods By employing THP-1 cells, co-culture systems of THP-1 cells and HTR-8/Svneo, HPVECs and Sprague–Dawley (SD) rats, in conjunction with gene knockdown and overexpression techniques, we explored the effects of GATA1 on the TrkB/cGMP–PKG signaling pathway. Transcriptomic sequencing, bioinformatics analysis, animal experiments, and clinical sample collection were conducted to validate the role of GATA1 in PE. Results Knockdown of GATA1 mitigated the symptoms of PE, and this effect was reversed by overexpression of TrkB. In comparison with the control group, the proportion of M2 cells elevated significantly in the sh-GATA1 group (P < 0.001). In addition, the protein expressions levels of TrkB, cGMP, and PKG were significantly decreased in the sh-GATA1 group were significantly decreased compared with those in the control group (P < 0.001, P < 0.001, P < 0.001, P < 0.05, respectively). Moreover, knockdown of GATA1 significantly promoted the migration rate and blood vessel formation of HTR-8/Svneo cells (P < 0.001, P < 0.05, respectively) which inhibited by overexpression of NTRK2 (P < 0.05, P < 0.01, respectively). Conclusions The study demonstrated that knockdown of GATA1 modulates M2 polarization of macrophage through the TrkB/cGMP–PKG signaling pathway, influencing the progression of PE. In addition, significant associations between GATA1 and the TrkB/cGMP–PKG signaling pathway were identified in the transcriptomic data from PE patient placentas.https://doi.org/10.1186/s40001-024-02229-0GATA1KnockdownNTRK2TrkBcGMP–PKGMacrophage |
| spellingShingle | Wushan Li Fei Hou Di Cheng Fengchun Gao Jin Wang Baoxia Cui GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia European Journal of Medical Research GATA1 Knockdown NTRK2 TrkB cGMP–PKG Macrophage |
| title | GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia |
| title_full | GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia |
| title_fullStr | GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia |
| title_full_unstemmed | GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia |
| title_short | GATA1-mediated macrophage polarization via TrkB/cGMP–PKG signaling pathway to promote the development of preeclampsia |
| title_sort | gata1 mediated macrophage polarization via trkb cgmp pkg signaling pathway to promote the development of preeclampsia |
| topic | GATA1 Knockdown NTRK2 TrkB cGMP–PKG Macrophage |
| url | https://doi.org/10.1186/s40001-024-02229-0 |
| work_keys_str_mv | AT wushanli gata1mediatedmacrophagepolarizationviatrkbcgmppkgsignalingpathwaytopromotethedevelopmentofpreeclampsia AT feihou gata1mediatedmacrophagepolarizationviatrkbcgmppkgsignalingpathwaytopromotethedevelopmentofpreeclampsia AT dicheng gata1mediatedmacrophagepolarizationviatrkbcgmppkgsignalingpathwaytopromotethedevelopmentofpreeclampsia AT fengchungao gata1mediatedmacrophagepolarizationviatrkbcgmppkgsignalingpathwaytopromotethedevelopmentofpreeclampsia AT jinwang gata1mediatedmacrophagepolarizationviatrkbcgmppkgsignalingpathwaytopromotethedevelopmentofpreeclampsia AT baoxiacui gata1mediatedmacrophagepolarizationviatrkbcgmppkgsignalingpathwaytopromotethedevelopmentofpreeclampsia |