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

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

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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).Depletion of CD147 also increased transcriptional expression and activity of γ-butyrobetaine hydroxylase(γ-BBD/BBOX1),a crucial molecule for carnitine metabolism,by inhibiting histone trimethylations of H3K9.Our findings demonstrate that CD147 is critical in metabolic reprogramming through the α-KG-H3K9me3-BBOX1 axis in the pathogenesis of psoriasis,indicating that epidermal CD147 is a promising target for psoriasis treatment.

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

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Department of Dermatology,Xiangya Hospital,Central South University,Changsha,Hunan,China

National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology,Changsha,Hunan,China

Furong Laboratory,Changsha,Hunan,China

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

National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South Universit

National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,Hunan,China

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国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金Science and Technology Innovation Program of Hunan ProvinceProgram of Introducing Talents of Discipline to Universities(111 Project)

8207345882221002821300908183009681974476821734242021RC4013B200 17

2024

10.34133/research.0167

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(1)
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