CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

作     者：Chao Chen Xiaoqing Yi Panpan Liu Jie Li Bei Yan Detian Zhang Lei Zhu Pian Yu Lei Li Jiaxiong Zhang Yehong Kuang Shuang Zhao Wu Zhu Cong Peng Xiang Chen Chao Chen;Xiaoqing Yi;Panpan Liu;Jie Li;Bei Yan;Detian Zhang;Lei Zhu;Pian Yu;Lei Li;Jiaxiong Zhang;Yehong Kuang;Shuang Zhao;Wu Zhu;Cong Peng;Xiang Chen

作者机构：Department of DermatologyXiangya HospitalCentral South UniversityChangshaHunanChina National Engineering Research Center of Personalized Diagnostic and Therapeutic TechnologyChangshaHunanChina Furong LaboratoryChangshaHunanChina Hunan Key Laboratory of Skin Cancer and PsoriasisHunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina 

出 版 物：《Research》 (研究（英文）)

年 卷 期：2024年第2023卷第1期

页      面：509-523页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：National Natural Science Grant Nos.82073458,82221002,82130090,81830096,81974476,and 82173424 the Science and Technology Innovation Program of Hunan Province(2021RC4013) the Program of Introducing Talents of Discipline to Universities(111 Project,No.B20017). 

主　　题：CD147 pathogenesis markedly 

摘      要：Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal cells.Although elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain unclear.We investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse models.In mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic inflammation.We found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in vivo.In CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147 s pivotal role in glycolysis reprogramming during pathogenesis of psoriasis.Using non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).