D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis
文献类型：期刊论文
| 作者 | Jing, Xiaoqi2; Wu, Jun3; Ning, Jingru4; Ding, Xiaoyu5; Du, Zhenyun2; Wang, Xiaojiang1; Huang, Lulin2; Wang, Ran3; Mei, Changlin3; Ding, Kan2,4,6 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2025-08-11 |
| 页码 | 13 |
| 关键词 | epidermal growth factor receptor epithelial-to-mesenchymal transition glucuronyl C5-epimerase kidney fibrosis |
| DOI | 10.1002/advs.202416216 |
| 英文摘要 | Renal tubular cells actively participate in fibrosis, leading to end-stage renal failure. However, the key molecules involved in fibrogenesis remain unclear. Glucuronyl C5-epimerase (Hsepi, gene name, Glce) is a key enzyme that catalyzes the biosynthesis of heparan sulfate (HS) chains attached to HS proteoglycans that are ubiquitously located on the cell membrane. Homozygous Glce-/- mice may exhibit embryonic lethality and multi-organ defects. However, the role of Glce in kidney fibrosis remains unclear. This study investigated the contribution of Glce to kidney development and its role in renal fibrosis pathogenesis. Here, it shows that Glce expression is significantly attenuated in the kidneys of patients with renal fibrosis and in animal models. Renal tubular-specific Glce deletion in mice exacerbated kidney fibrosis, while AAV-mediated Glce overexpression in unilateral ureteral obstruction-treated mice ameliorated kidney fibrosis via the TGF-beta/Smad2/3 signaling pathway. Mechanistic studies indicate that Glce protein may bind to epidermal growth factor receptor (EGFR) to inactivate EGFR/ERK signaling and further impede TGF-beta/Smad signaling pathway and renal fibrosis in Glce-/- and wild-type mice. Notably, the anti-fibrotic function is independent of Glce enzymatic activation. These findings reveal a novel function of Glce, which plays a key role in kidney fibrosis. |
| WOS关键词 | TO-MESENCHYMAL TRANSITION ; CELL CYCLE ARREST ; RENAL FIBROSIS ; FIBROBLASTS ; MECHANISMS ; DRIVES ; ROLES ; NOTCH |
| 资助项目 | Shanghai Municipal Science and Technology Major Project, National Key R&D Program of China ; National Natural Science Foundation of China[32271332] ; National Natural Science Foundation of China[31870801] ; National Natural Science Foundation of China[2019B090904008] ; High-level Innovative Research Institute[2021B0909050003] ; Department of Science and Technology of Guangdong Province ; Zhongshan Municipal Bureau of Science and Technology ; [2022YFA1303802] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001546758200001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321234]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Mei, Changlin; Ding, Kan |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Dept Nat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Second Mil Med Univ, Changzheng Hosp, Dept Nephrol, Shanghai 201203, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 6.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jing, Xiaoqi,Wu, Jun,Ning, Jingru,et al. D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis[J]. ADVANCED SCIENCE,2025:13. |
| APA | Jing, Xiaoqi.,Wu, Jun.,Ning, Jingru.,Ding, Xiaoyu.,Du, Zhenyun.,...&Ding, Kan.(2025).D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis.ADVANCED SCIENCE,13. |
| MLA | Jing, Xiaoqi,et al."D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis".ADVANCED SCIENCE (2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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