ArticleRedox biology2026
Stromal cell-derived itaconate promotes endometriosis via macrophage NRF2 and lysosomal pH modulation.
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Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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Who cites it
2 citing papers in PubMed.
- ACOD1 deficiency promotes DDX1 methylation-mediated mitochondrial dysfunction and dermal papilla cell senescence in androgenetic alopecia.BMC medicine · 2026Article
- From local lesion to multisystem disease: integrated crosstalk among the gut microbiota, immune system, and host metabolism in endometriosis.Frontiers in immunology · 2026Review
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Authors and funding
15 authors.
Zhaoyang ZhongDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250000, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Shuang WangDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250000, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Qianhui RenDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Xue JiaoDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250000, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Le XuDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Xiaoyu DongDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Na LiDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Hongwei GuanDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Ran ChuDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Ming YuanDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China.
Jincheng LiuState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China.
Yanbo DuMedical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China.
Keke WeiState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. Electronic address: 18627918831@163.com.
Lei YanMedical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. Electronic address: yanlei@sdu.edu.cn.
Guoyun WangDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250000, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction) Shandong Provincial Health Commission Key Laboratory of Prevention and Treatment for Major Mynecological Diseases (Under Construction), China; JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China; Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China. Electronic address: wangguoy@sdu.edu.cn.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endometriosis (EM) is driven by immune dysregulation and macrophage dysfunction, yet the underlying mechanisms remain unclear. Here, metabolomic profiling revealed excessive itaconate accumulation in EM lesions, primarily due to elevated cis-aconitate decarboxylase 1 (ACOD1) expression in ectopic stromal cells (ESCs). ESC-derived itaconate was internalized by peritoneal macrophages, where it suppressed pro-inflammatory activity and phagocytosis, thereby facilitating ESC survival and dissemination. Mechanistically, itaconate exerted dual regulatory effects on macrophages: it activated NRF2 signaling to repress the transcription of pro-inflammatory genes, and it enhanced lysosomal acidification, thereby reducing lysosomal calcium release, which in turn inhibited p38-MAPK activation and further attenuated pro-inflammatory gene expression. In vivo, ACOD1 inhibition restored macrophage function and reduced lesion burden, while exogenous 4-octyl itaconate aggravated disease progression. These findings define a novel "ESC-ACOD1-itaconate-macrophage" axis that mediates immunosuppression in EM and identify ACOD1 as potential therapeutic targets.
Indexed as
EndometriosisLysosomesMacrophagesNF-E2-Related Factor 2Stromal CellsSuccinatesAnimalsCarboxy-LyasesFemaleHumansHydrogen-Ion ConcentrationHydro-LyasesMicePhagocytosisSignal TransductionACOD1 protein, humanAcod1 protein, mouseCarboxy-LyasesHydro-Lyasesitaconic acidNF-E2-Related Factor 2SuccinatesACOD1EndometriosisItaconateLysosomeMacrophage
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