首页|Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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  • 国家科技期刊平台
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Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Molecular targetsProEGCGEGCGAngiogenesisTreatmentEndometriosis

Sze Wan Hung、Massimiliano Gaetani、Yiran Li、Zhouyurong Tan、Xu Zheng、Ruizhe Zhang、Yang Ding、Gene Chi Wai Man、Tao Zhang、Yi Song、Yao Wang、Jacqueline Pui Wah Chung、Tak Hang Chan、Roman A.Zubarev、Chi Chiu Wang

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Department of Obstetrics & Gynaecology,The Chinese University of Hong Kong,Hong Kong,China

Division of Physiological Chemistry I,Department of Medical Biochemistry and Biophysics,Karolinska Institutet,Stockholm,SE 17177,Sweden

Chemical Proteomics Core Facility,Department of Medical Biochemistry and Biophysics,Karolinska Institutet,Stockholm,SE 17177,Sweden

Unit of Chemical Proteomics,Science for Life Laboratory(SciLifeLab),Stockholm,SE 17177,Sweden

Center for Reproductive Medicine,Henan Key Laboratory of Reproduction and Genetics,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,450003,China

Department of Chemistry,McGill University,Montreal,H3A2K6,Canada

Department of Pharmacological & Technological Chemistry,I.M.Sechenov First Moscow State Medical University,Moscow,119146,Russia

Reproduction and Development,Li Ka Shing Institute of Health Sciences,The Chinese University of Hong Kong,Hong Kong,China

School of Biomedical Sciences,The Chinese University of Hong Kong,Hong Kong,China

Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine,The Chinese University of Hong Kong,Hong Kong,China

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GRF RGC & CRF,Hong KongGRF RGC & CRF,Hong KongHMRF,Hong KongITF,Hong KongUGC DirectUGC DirectUGC DirectHKOG Trust Fund(2011、2014、2019)国家自然科学基金国家自然科学基金Chemical proteomics core facility at Biomedicum(MBB,Karolinska Institute)Unit of SciLifeLab and part of the Swedish National Infrastructure for Biological Mass Spectrometry(BioMS)

475012C5045-20 EF03141386ITS/209/12201120122021.0328197422582201823

2024

10.1016/j.jpha.2023.09.005

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(1)
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