1. Academic Validation
  2. Apelin Receptor can Act as a Specific Marker and Promising Therapeutic Target for Infantile Hemangioma

Apelin Receptor can Act as a Specific Marker and Promising Therapeutic Target for Infantile Hemangioma

  • J Invest Dermatol. 2022 Oct 12;S0022-202X(22)02643-4. doi: 10.1016/j.jid.2022.09.657.
Qianyi Chen 1 Hanru Ying 1 Zhang Yu 1 Lei Chang 1 Zongan Chen 1 Jialin Chen 1 Shih-Jen Chang 1 Yajing Qiu 1 Xiaoxi Lin 2
Affiliations

Affiliations

  • 1 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
  • 2 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; Department of Laser and Aesthetic Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address: linxiaoxi@126.com.
Abstract

Infantile hemangioma (IH), the most common benign tumor in infancy, is generally sensitive to propranolol treatment. However, the challenge remains as resistance or recurrence could occur in some patients, and the mechanism or target of propranolol remains unknown. Therefore, a novel drug is needed. In this study, we explored whether apelin receptor (APJ) can become a candidate target. We found that APJ is expressed only in endothelial cells of IH (HemECs) but not in Other vascular anomalies, and its antagonist, ML221, can negatively regulate cellular viability and functions of HemECs. This inhibitory effect could be replicated in a murine hemangioma model. Importantly, in vitro experiments also indicated that ML221 failed to affect the proliferation or angiogenesis of normal endothelial cells or APJ-knockout HemECs. Through analysis of the phospho-antibody microarray data, ML221 was revealed to have an inhibitory effect on HemECs by suppressing the activation of MAPK/ERK pathway. These results verified the distinctive expression of APJ in IH and specific inhibition of HemEC activity caused by ML221. Besides, APJ was also detected in propranolol-resistant IH. Collectively, we propose that APJ can act as a specific marker and promising therapeutic target for IH, which will facilitate further drug development.

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