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 

机构地区：[1]Department of Dermatology,Xiangya Hospital,Central South University,Changsha,Hunan,China [2]National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology,Changsha,Hunan,China [3]Furong Laboratory,Changsha,Hunan,China [4]Hunan Key Laboratory of Skin Cancer and Psoriasis,Hunan Engineering Research Center of Skin Health and Disease,Xiangya Hospital,Central South University,Changsha,Hunan,China [5]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,Hunan,China

出　　处：《Research》2024年第1期509-523,共15页研究（英文）

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).

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).

关 键 词：CD147 PATHOGENESIS markedly 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]