ALKBH5通过促进血管生成加重小鼠银屑病皮炎。

IF 3.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Chengfang Zhang, Fei Li, Bao Chai, Jian Jiang, Yinlian Zhang, Xuemei Li, Jingyu Zhang, Yuqiong Huang, Zilin Jin, Yixuan Wang Wan, Suwen Liu, Nan Yu, Hongxiang Chen
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引用次数: 0

摘要

银屑病是一种慢性炎症性皮肤病,其发病机制在很大程度上与血管生成异常有关。先前的研究表明,AlkB同源物5 (ALKBH5)是影响n6 -甲基腺苷(m6A)修饰的重要去甲基化酶,在心血管和眼病中起调节血管生成的作用。本研究发现,与对照组相比,IMQ组皮肤中ALKBH5表达上调并与CD31共定位。alkbh5缺陷小鼠减轻了imq诱导的银屑病皮炎,并表现出组织学改善,包括表皮厚度减少、角化过度、真皮毛细血管数量减少和炎症细胞浸润。ALKBH5-KO小鼠通过下调蛋白激酶B (AKT)/雷帕霉素(mTOR)通路的哺乳动物靶点来减轻银屑病病变的血管生成。此外,il - 17a诱导的人脐静脉内皮细胞(HUVECs)中ALKBH5的表达显著上调,进一步促进血管生成相关细胞因子的表达和内皮细胞的增殖。ALKBH5敲低组细胞增殖和血管生成受到抑制,而ALKBH5过表达组细胞增殖和血管生成受到促进。ALKBH5通过AKT-mTOR通路促进了HUVECs血管生成的调控。总之,ALKBH5在银屑病皮炎和血管生成中起关键作用,可能为银屑病治疗提供新的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ALKBH5 exacerbates psoriatic dermatitis in mice by promoting angiogenesis.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N6-methyladenosine (m6A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.

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来源期刊
Frontiers of Medicine
Frontiers of Medicine ONCOLOGYMEDICINE, RESEARCH & EXPERIMENTAL&-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
18.30
自引率
0.00%
发文量
800
期刊介绍: Frontiers of Medicine is an international general medical journal sponsored by the Ministry of Education of China. The journal is jointly published by the Higher Education Press and Springer. Since the first issue of 2010, this journal has been indexed in PubMed/MEDLINE. Frontiers of Medicine is dedicated to publishing original research and review articles on the latest advances in clinical and basic medicine with a focus on epidemiology, traditional Chinese medicine, translational research, healthcare, public health and health policies.
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