2. Academic Validation
  3. R-Propranolol Promotes the Adipogenesis and Subsequent Apoptosis of Hemangioma Stem Cells through the Protein Kinase RNA-Like Endoplasmic Reticulum Kinase Signaling Pathway

R-Propranolol Promotes the Adipogenesis and Subsequent Apoptosis of Hemangioma Stem Cells through the Protein Kinase RNA-Like Endoplasmic Reticulum Kinase Signaling Pathway

  • Am J Pathol. 2026 Jun;196(6):1389-1401. doi: 10.1016/j.ajpath.2026.02.008.
Suyang Chen 1,  Rong Wang 2,  Yanyu Guo 1,  Shaodong Yang 3,  Guoyong Tong 4,  Yu Sun 5,  Xiaoshun Zhou 6,  Dongsheng Mou 6,  Wenqun Zhong 7,  Yu Cai 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 2 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 3 Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 4 Department of Stomatology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.
  • 5 Department of Plastic Surgery, Wuhan Children's Hospital, Wuhan, China.
  • 6 Wuhan Conform Pharm Co., Ltd., Wuhan, China.
  • 7 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: [email protected].
  • 8 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: [email protected].
PMID: 41864339 DOI: 10.1016/j.ajpath.2026.02.008
Abstract

Propranolol is currently the first-line therapy for infantile hemangioma (IH); however, its use is limited by notable adverse effects. The non-β-blocker enantiomer of propranolol, R-propranolol, represents a promising alternative for IH treatment. In this study, the efficacy of R-propranolol and its underlying mechanism in IH involution were investigated. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway was required for the adipogenic potential of hemangioma stem cells (HemSCs), whereas prolonged PERK activation led to Apoptosis. R-propranolol and racemic propranolol induce comparable HemSC adipogenesis. R-propranolol showed a stronger ability to disrupt protein homeostasis in HemSCs than racemic propranolol, as indicated by increased protein misfolding and enhanced activation of the PERK signaling pathway. Notably, R-propranolol induced HemSC Apoptosis more effectively than racemic propranolol. This effect was attenuated by the PERK Inhibitor GSK2606414. Immunostaining of clinical specimens further showed that PERK expression was higher in involuting IH samples than in proliferating IH samples. Together, these findings demonstrate that R-propranolol promotes adipogenesis and subsequent Apoptosis of HemSCs through activation of the PERK signaling pathway.

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