2. Academic Validation
  3. ALKBH5 exacerbates psoriatic dermatitis in mice by promoting angiogenesis

ALKBH5 exacerbates psoriatic dermatitis in mice by promoting angiogenesis

  • Front Med. 2025 Jun 16. doi: 10.1007/s11684-025-1147-1.
Chengfang Zhang # 1 2 3,  Fei Li # 4,  Bao Chai # 2,  Jian Jiang 5,  Yinlian Zhang 6 7,  Xuemei Li 2 8,  Jingyu Zhang 2,  Yuqiong Huang 5,  Zilin Jin 5,  Yixuan Wang Wan 5,  Suwen Liu 5,  Nan Yu 9,  Hongxiang Chen 10 11 12 13
Affiliations

Affiliations

  • 1 Ningxia Medical University, Yinchuan, 750004, China.
  • 2 Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital/The 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China.
  • 3 Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
  • 4 Department of Cosmetic Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital/The 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China.
  • 5 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 6 Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518055, China.
  • 7 Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 8 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China.
  • 9 Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, 750004, China. 13895095009@163.com.
  • 10 Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. hongxiangchen@hotmail.com.
  • 11 Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital/The 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China. hongxiangchen@hotmail.com.
  • 12 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. hongxiangchen@hotmail.com.
  • 13 Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, 750004, China. hongxiangchen@hotmail.com.
  • # Contributed equally.
PMID: 40522618 DOI: 10.1007/s11684-025-1147-1
Abstract

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.

Keywords

AKT/mTOR signaling pathway; ALKBH5; angiogenesis; m6A; psoriasis.

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