The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease
Abstract Interstitial fibrosis after acute kidney injury is an ongoing pathological process of chronic inflammatory injury and repair. Macrophages participate in renal inflammation, repair and fibrosis by continuously changing their phenotype and function. The tissue microenvironment of kidney injur...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-025-00746-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849329406747607040 |
|---|---|
| author | Na Gong Wenjuan Wang Yifei Fu Xumin Zheng Xinru Guo Yuhao Chen Yan Chen Shengchun Zheng Guangyan Cai |
| author_facet | Na Gong Wenjuan Wang Yifei Fu Xumin Zheng Xinru Guo Yuhao Chen Yan Chen Shengchun Zheng Guangyan Cai |
| author_sort | Na Gong |
| collection | DOAJ |
| description | Abstract Interstitial fibrosis after acute kidney injury is an ongoing pathological process of chronic inflammatory injury and repair. Macrophages participate in renal inflammation, repair and fibrosis by continuously changing their phenotype and function. The tissue microenvironment of kidney injury induces changes in key metabolic enzymes, pathways and metabolites in macrophages, leading to phenotypic and functional conversions, but the detailed mechanisms are unclear. However, in the early phase of acute kidney injury, macrophages shift to a pro-inflammatory role relying on glycolysis and pentose phosphate pathways. The tissue microenvironment regulates the suppression of glycolysis-related genes and the up-regulation of oxidative phosphorylation and tricarboxylic acid cycle genes in macrophages, resulting in a gradual shift to an anti-inflammatory phenotype, which is involved in tissue repair and remodelling. In the late stage of injury, if macrophages continue to be overactive, they will be involved in renal fibrosis. The concomitant enhancement of nucleotide and amino acid metabolism, especially arginine and glutamine metabolism, is critical for the macrophage function and phenotypic transition during the above injury process. Macrophage metabolic reprogramming therefore provides new therapeutic targets for intervention in inflammatory injury and interstitial fibrosis in kidney disease. |
| format | Article |
| id | doaj-art-8ec2563467cc4389a581e2b48e0fda39 |
| institution | Kabale University |
| issn | 1689-1392 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj-art-8ec2563467cc4389a581e2b48e0fda392025-08-20T03:47:16ZengBMCCellular & Molecular Biology Letters1689-13922025-06-0130113010.1186/s11658-025-00746-2The crucial role of metabolic reprogramming in driving macrophage conversion in kidney diseaseNa Gong0Wenjuan Wang1Yifei Fu2Xumin Zheng3Xinru Guo4Yuhao Chen5Yan Chen6Shengchun Zheng7Guangyan Cai8Medical School of Chinese PLADepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine(Zyyzdxk-2023310)Medical School of Chinese PLAMedical School of Chinese PLASchool of Medicine, Nankai UniversityMedical School of Chinese PLAMedical School of Chinese PLAMedical School of Chinese PLADepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine(Zyyzdxk-2023310)Abstract Interstitial fibrosis after acute kidney injury is an ongoing pathological process of chronic inflammatory injury and repair. Macrophages participate in renal inflammation, repair and fibrosis by continuously changing their phenotype and function. The tissue microenvironment of kidney injury induces changes in key metabolic enzymes, pathways and metabolites in macrophages, leading to phenotypic and functional conversions, but the detailed mechanisms are unclear. However, in the early phase of acute kidney injury, macrophages shift to a pro-inflammatory role relying on glycolysis and pentose phosphate pathways. The tissue microenvironment regulates the suppression of glycolysis-related genes and the up-regulation of oxidative phosphorylation and tricarboxylic acid cycle genes in macrophages, resulting in a gradual shift to an anti-inflammatory phenotype, which is involved in tissue repair and remodelling. In the late stage of injury, if macrophages continue to be overactive, they will be involved in renal fibrosis. The concomitant enhancement of nucleotide and amino acid metabolism, especially arginine and glutamine metabolism, is critical for the macrophage function and phenotypic transition during the above injury process. Macrophage metabolic reprogramming therefore provides new therapeutic targets for intervention in inflammatory injury and interstitial fibrosis in kidney disease.https://doi.org/10.1186/s11658-025-00746-2InflammationInjury and repairKidney fibrosisMacrophagesMetabolic reprogramming |
| spellingShingle | Na Gong Wenjuan Wang Yifei Fu Xumin Zheng Xinru Guo Yuhao Chen Yan Chen Shengchun Zheng Guangyan Cai The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease Cellular & Molecular Biology Letters Inflammation Injury and repair Kidney fibrosis Macrophages Metabolic reprogramming |
| title | The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease |
| title_full | The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease |
| title_fullStr | The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease |
| title_full_unstemmed | The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease |
| title_short | The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease |
| title_sort | crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease |
| topic | Inflammation Injury and repair Kidney fibrosis Macrophages Metabolic reprogramming |
| url | https://doi.org/10.1186/s11658-025-00746-2 |
| work_keys_str_mv | AT nagong thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT wenjuanwang thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT yifeifu thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT xuminzheng thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT xinruguo thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT yuhaochen thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT yanchen thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT shengchunzheng thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT guangyancai thecrucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT nagong crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT wenjuanwang crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT yifeifu crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT xuminzheng crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT xinruguo crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT yuhaochen crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT yanchen crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT shengchunzheng crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease AT guangyancai crucialroleofmetabolicreprogrammingindrivingmacrophageconversioninkidneydisease |