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VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway

Signal Transduction and Targeted Therapy 2023年第9期8卷 4380-4393页

作者： Chunsik Lee Rongyuan Chen Guangli Sun Xialin Liu Xianchai Lin Chang He Liying Xing Lixian Liu Lasse DJensen Anil Kumar harald flanger Xiangrong Ren Jianing Zhang Lijuan Huang Xiangke Yin JongKyong Kim Juanhua Zhu Guanqun Huang Jiani Li Weiwei Lu Wei Chen Juanxi Liu Jiaxin Hu Qihang Sun Weisi Lu Lekun Fang Shasha Wang Haiqing Kuang Yihan Zhang Geng Tian Jia Mi Bi-Ang Kang Masashi Narazaki Aaron Prodeus Luc Schoonjans David MOrnitz Jean Gariepy Guy Eelen Mieke Dewerchin Yunlong Yang Jing-Song Ou Antonio Mora Jin Yao Chen Zhao Yizhi Liu Peter Carmeliet Yihai Cao Xuri Li State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen University and Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060P.R.China Affiliated Eye Hospital of Nanjing Medical University Nanjing 210000China Department of Obstetrics and Gynecology Guangdong Provincial Key Laboratory of Major Obstetric DiseasesGuangdong Provincial Clinical Research Center for Obstetrics and GynecologyThe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Shenzhen Eye Hospital Jinan UniversityShenzhen Eye InstituteShenzhenChina Department of Health Medical and Caring SciencesDivision of Diagnostics and Specialist MedicineLinköping University58183 LinköpingSweden Department of Cardiology AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany DZHK(German Research Centre for Cardiovascular Research) partner site Mannheim/HeidelbergMannheimGermany European Center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease Guangdong Research Institute of GastroenterologyDepartment of Colorectal SurgeryThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Eye Institute Eye and ENT HospitalShanghai Medical CollegeFudan UniversityKey Laboratory of Myopia of State Health Ministry(Fudan University)and Shanghai Key Laboratory of Visual Impairment and Restoration200031 ShanghaiChina Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical UniversityYantai 264003P.R.China Division of Cardiac Surgery National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular DiseasesNHC key Laboratory of Assisted Circulation(Sun Yat-sen University)The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Respiratory Medicine and Clinical Imm

Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different ***,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular *** is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying *** comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly ***,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor *** work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 *** the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

关键词： FGFR1 FGF2 drugs

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