The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis
Background: Endometriosis (EM) is a prevalent gynecological disorder in women. Although the underlying mechanisms have yet to be fully elucidated, EM may be related to oxidative stress. The current research aimed to identify possible pathways that control oxidative stress in EM, t...
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IMR Press
2025-05-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/30/5/10.31083/FBL33488 |
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| author | Jing Su Peipei Tang Jixiang Zhong Rongxue Zhang Huiying Xue Hong Zhang |
| author_facet | Jing Su Peipei Tang Jixiang Zhong Rongxue Zhang Huiying Xue Hong Zhang |
| author_sort | Jing Su |
| collection | DOAJ |
| description | Background: Endometriosis (EM) is a prevalent gynecological disorder in women. Although the underlying mechanisms have yet to be fully elucidated, EM may be related to oxidative stress. The current research aimed to identify possible pathways that control oxidative stress in EM, thereby providing a theoretical foundation for its clinical diagnosis and treatment. Methods: High-throughput RNA sequencing (RNA-seq) data were integrated with GeneCards online data to screen for oxidative stress-related genes and potential targets in EM. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry assays confirmed the expression of candidate genes. The in vivo and in vitro effects of CCAAT enhancer binding protein delta (CEBPD, C/EBP-delta) and DNA damage-inducible transcript 4 (DDIT4) on oxidative stress, cell proliferation, and angiogenesis in endometriotic cells were validated using loss- or gain-of-function approaches. Results: CEBPD was highly expressed in ectopic and eutopic endometrial tissue from patients with endometriosis. Loss- or gain-of-function experiments showed that CEBPD promoted oxidative stress, cell proliferation, and angiogenesis in vitro and in vivo. Integration of RNA-seq and online data revealed that CEBPD regulates DDIT4 expression, subsequently increasing oxidative stress, cell proliferation, and angiogenesis in endometriotic cells. Finally, CEBPD and DDIT4 were found to regulate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) proteins associated with the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions: These results suggest that CEBPD may promote oxidative stress, cell proliferation, and angiogenesis in EM by activating MAPK via DDIT4. Hence, CEBPD may be a potential target for diagnosing and treating EM. |
| format | Article |
| id | doaj-art-9778a18f8a3c4183b7acde0344456219 |
| institution | OA Journals |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | IMR Press |
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| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-9778a18f8a3c4183b7acde03444562192025-08-20T02:03:00ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-05-013053348810.31083/FBL33488S2768-6701(25)01718-6The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in EndometriosisJing Su0Peipei Tang1Jixiang Zhong2Rongxue Zhang3Huiying Xue4Hong Zhang5Department of Reproductive Medicine, The Second Affiliated Hospital of Soochow University, 215004 Suzhou, Jiangsu, ChinaThe Digestive and Reproductive System Cancers Precise Prevention Engineering Research Center of Jiangsu Province, Jiangsu College of Nursing, 223002 Huai’an, Jiangsu, ChinaDepartment of Reproductive Medicine, Huai’an Maternity and Child Health Care Hospital Affiliated to Yangzhou University, 223002 Huai’an, Jiangsu, ChinaDepartment of Reproductive Medicine, Huai’an Maternity and Child Health Care Hospital Affiliated to Yangzhou University, 223002 Huai’an, Jiangsu, ChinaDepartment of Reproductive Medicine, Huai’an Maternity and Child Health Care Hospital Affiliated to Yangzhou University, 223002 Huai’an, Jiangsu, ChinaDepartment of Reproductive Medicine, The Second Affiliated Hospital of Soochow University, 215004 Suzhou, Jiangsu, ChinaBackground: Endometriosis (EM) is a prevalent gynecological disorder in women. Although the underlying mechanisms have yet to be fully elucidated, EM may be related to oxidative stress. The current research aimed to identify possible pathways that control oxidative stress in EM, thereby providing a theoretical foundation for its clinical diagnosis and treatment. Methods: High-throughput RNA sequencing (RNA-seq) data were integrated with GeneCards online data to screen for oxidative stress-related genes and potential targets in EM. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry assays confirmed the expression of candidate genes. The in vivo and in vitro effects of CCAAT enhancer binding protein delta (CEBPD, C/EBP-delta) and DNA damage-inducible transcript 4 (DDIT4) on oxidative stress, cell proliferation, and angiogenesis in endometriotic cells were validated using loss- or gain-of-function approaches. Results: CEBPD was highly expressed in ectopic and eutopic endometrial tissue from patients with endometriosis. Loss- or gain-of-function experiments showed that CEBPD promoted oxidative stress, cell proliferation, and angiogenesis in vitro and in vivo. Integration of RNA-seq and online data revealed that CEBPD regulates DDIT4 expression, subsequently increasing oxidative stress, cell proliferation, and angiogenesis in endometriotic cells. Finally, CEBPD and DDIT4 were found to regulate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) proteins associated with the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions: These results suggest that CEBPD may promote oxidative stress, cell proliferation, and angiogenesis in EM by activating MAPK via DDIT4. Hence, CEBPD may be a potential target for diagnosing and treating EM.https://www.imrpress.com/journal/FBL/30/5/10.31083/FBL33488endometriosisccaat-enhancer-binding protein-deltaoxidative stresscell proliferationangiogenesis |
| spellingShingle | Jing Su Peipei Tang Jixiang Zhong Rongxue Zhang Huiying Xue Hong Zhang The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis Frontiers in Bioscience-Landmark endometriosis ccaat-enhancer-binding protein-delta oxidative stress cell proliferation angiogenesis |
| title | The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis |
| title_full | The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis |
| title_fullStr | The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis |
| title_full_unstemmed | The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis |
| title_short | The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis |
| title_sort | role of cebpd in oxidative stress and angiogenesis regulation in endometriosis |
| topic | endometriosis ccaat-enhancer-binding protein-delta oxidative stress cell proliferation angiogenesis |
| url | https://www.imrpress.com/journal/FBL/30/5/10.31083/FBL33488 |
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