Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome
Abstract Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301+ macrophages...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202317601 |
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| author | Haining Lv Haixiang Sun Limin Wang Simin Yao Dan Liu Xiwen Zhang Zhongrui Pei Jianjun Zhou Huiyan Wang Jianwu Dai Guijun Yan Lijun Ding Zhiyin Wang Chenrui Cao Guangfeng Zhao Yali Hu |
| author_facet | Haining Lv Haixiang Sun Limin Wang Simin Yao Dan Liu Xiwen Zhang Zhongrui Pei Jianjun Zhou Huiyan Wang Jianwu Dai Guijun Yan Lijun Ding Zhiyin Wang Chenrui Cao Guangfeng Zhao Yali Hu |
| author_sort | Haining Lv |
| collection | DOAJ |
| description | Abstract Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301+ macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single‐cell RNA sequencing, bulk RNA sequencing, and experimental verification. Increasing CD301+ macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts and resulted in extracellular matrix accumulation, which destroyed the physiological architecture of endometrial tissue, drove endometrial fibrosis, and ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, CD301+ macrophages secreted GAS6 to activate the AXL/NF‐κB pathway, upregulating the profibrotic protein synthesis. Targeted deletion of CD301+ macrophages or inhibition of AXL by Bemcentinib blunted the pathology and improved the outcomes of pregnancy in mice, supporting the therapeutic potential of targeting CD301+ macrophages for treating endometrial fibrosis. |
| format | Article |
| id | doaj-art-140882d6042c44ef84d10e0a062db737 |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-140882d6042c44ef84d10e0a062db7372025-08-20T03:05:53ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-07-0115911910.15252/emmm.202317601Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcomeHaining Lv0Haixiang Sun1Limin Wang2Simin Yao3Dan Liu4Xiwen Zhang5Zhongrui Pei6Jianjun Zhou7Huiyan Wang8Jianwu Dai9Guijun Yan10Lijun Ding11Zhiyin Wang12Chenrui Cao13Guangfeng Zhao14Yali Hu15Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityInstitute of Genetics and Developmental Biology, Chinese Academy of SciencesCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301+ macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single‐cell RNA sequencing, bulk RNA sequencing, and experimental verification. Increasing CD301+ macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts and resulted in extracellular matrix accumulation, which destroyed the physiological architecture of endometrial tissue, drove endometrial fibrosis, and ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, CD301+ macrophages secreted GAS6 to activate the AXL/NF‐κB pathway, upregulating the profibrotic protein synthesis. Targeted deletion of CD301+ macrophages or inhibition of AXL by Bemcentinib blunted the pathology and improved the outcomes of pregnancy in mice, supporting the therapeutic potential of targeting CD301+ macrophages for treating endometrial fibrosis.https://doi.org/10.15252/emmm.202317601CD301+ macrophagesendometrial fibrosisintrauterine adhesionpregnancy outcome |
| spellingShingle | Haining Lv Haixiang Sun Limin Wang Simin Yao Dan Liu Xiwen Zhang Zhongrui Pei Jianjun Zhou Huiyan Wang Jianwu Dai Guijun Yan Lijun Ding Zhiyin Wang Chenrui Cao Guangfeng Zhao Yali Hu Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome EMBO Molecular Medicine CD301+ macrophages endometrial fibrosis intrauterine adhesion pregnancy outcome |
| title | Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
| title_full | Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
| title_fullStr | Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
| title_full_unstemmed | Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
| title_short | Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
| title_sort | targeting cd301 macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
| topic | CD301+ macrophages endometrial fibrosis intrauterine adhesion pregnancy outcome |
| url | https://doi.org/10.15252/emmm.202317601 |
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