2. Academic Validation
  3. Irisin alleviates steroid-induced vascular dysfunction by regulating the αVβ5-c-Abl-Caveolin-1 signaling pathway

Irisin alleviates steroid-induced vascular dysfunction by regulating the αVβ5-c-Abl-Caveolin-1 signaling pathway

  • Biochem Pharmacol. 2025 Mar 12:236:116870. doi: 10.1016/j.bcp.2025.116870.
Lijun Fang 1,  Wenqiang Li 2,  Hua Zhao 3,  Wei Wang 4,  Hongmei Gao 5,  Pengqi Wang 6,  Xinzhi Zhang 6,  Ruijuan Lv 7,  Feng Xu 8,  Jiazheng Chen 9,  Linmao Lyu 10,  Yuguo Chen 11
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Department of Emergency Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 3 Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.
  • 4 School of Public Health, Shandong University, Jinan, China.
  • 5 Department of Cardiology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
  • 6 Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 7 Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
  • 8 Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: xufengsdu@126.com.
  • 9 Department of Orthopaedics, Peking University Third Hospital, Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China. Electronic address: doctorcjz@163.com.
  • 10 Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: linmao.lyu@sdu.edu.cn.
  • 11 Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: chen919085@sdu.edu.cn.
PMID: 40086515 DOI: 10.1016/j.bcp.2025.116870
Abstract

Steroid-induced avascular necrosis of the femoral head (SANFH) is a progressive degenerative disease of the hip, primarily due to glucocorticoid (GC)-induced endothelial cell (EC) injury and compromised blood supply. Irisin is an EC-protective mytokine whose receptor is the Integrin αVβ5. Caveolin-1 (CAV-1)， a major component of caveolae, causes endothelial dysfunction when phosphorylated. However, the role of irisin and CAV-1 in SANFH remains unclear. In our study, irisin levels decreased but CAV-1 phosphorylation increased in human and mouse SANFH samples. Intraperitoneal irisin injection (250 μg/kg daily) notably reduced GC-induced osteonecrosis, vascular abnormalities, and CAV-1 phosphorylation in SANFH mice. In cultured ECs, GC induced CAV-1 phosphorylation by activating c-Abl via the Glucocorticoid Receptor, and irisin inhibited GC-induced phosphorylation of c-Abl and CAV-1 via the Integrin αVβ5. Inhibition of Integrin αVβ5 also abolished the protective effects of irisin on ERK and eNOS signalling, viability, angiogenesis, and migration in ECs. Therefore, our findings indicate that irisin has a protective role against vascular dysfunction in SANFH, possibly mediated by the inhibition of GC-triggered c-Abl-CAV-1 phosphorylation through Integrin αVβ5. These findings provide insights into the potential therapeutic applications of irisin in SANFH.

Keywords

Caveolin-1; Glucocorticoid; Irisin; Steroid-induced avascular necrosis of femoral head; Vascular dysfunction.

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