ArticleActa pharmaceutica Sinica. B2026
Direct pharmacological targeting of RAC1 by chlorogenic acid: A novel therapeutic approach for mesangial proliferative glomerulonephritis.
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22 authors.
Yilun QuSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Lingling WuSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Yong WangSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Fei PengSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Jie ZhangSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Dan PanSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Tiantian WangSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Yena ZhouSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Jikai XiaSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Jiayi HeClinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
Chunru ShiSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Yinghua ZhaoBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.
Xu WangSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Ran LiuSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Yingjie ZhangSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Jiaona LiuSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Jie WuSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Shuwei DuanSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Guangyan CaiSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Ping LiSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Quan HongSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Xiangmei ChenSenior Department of Nephrology, 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, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Beijing 100853, China.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesangial proliferative glomerulonephritis (MsPGN) is a common cause of end-stage renal disease, characterized by mesangial cell proliferation within glomeruli. Mesangial cell activation triggered by inflammation is a key factor in the development of MsPGN. However, effective therapeutic strategies targeting this process are still limited. Here, we uncovered, for the first time, the direct effects of chlorogenic acid (CGA), a naturally occurring small-molecule compound with anti-inflammatory and antiproliferative properties, on mesangial cells in an anti-Thy1 nephritis animal model. A multi-dimensional pharmacological platform integrating laser microdissection-coupled glomerular proteomics affinity deconvolution, surface plasmon resonance, molecular dynamics, and enzyme assays identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as the direct target of CGA. Mechanistically, CGA competitively binds to the LYS15, PRO33, and THR34 amino acid residues-located within residues 57-65 of the GTP/GDP-binding domain of RAC1, inhibiting its activation and subsequently reducing AKT phosphorylation while suppressing Thrombospondin-1 secretion from mesangial cells-a key ligand for macrophage CD36 receptors. This interaction deactivates macrophages and lowers the levels of inflammatory cytokines, including TNF
Indexed as
AKTCD36Chlorogenic acidInflammatory responseMesangial cell activationMesangial proliferative glomerulonephritisRAC1Thrombospondin-1
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