Macrophage scavenger receptor A1 promotes skeletal muscle regeneration after hindlimb ischemia
Siying Wang1
Saiya Wang1
Wenhan Cai1
Jie Wang1
Jianan Huang1
Qing Yang1
Hui Bai2
Bin Jiang2
Jingjing Ben2
Hanwen Zhang2
Xudong Zhu2
Xiaoyu Li1
Qi Chen2
1.Department of Pathophysiology,Key Laboratory of Targeted Intervention of Cardiovascular Disease and Molecular Intervention,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Pathophysiology,Key Laboratory of Targeted Intervention of Cardiovascular Disease and Molecular Intervention,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China;The Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou Municipal Hospital,Gusu School,Nanjing Medical University,Nanjing,Jiangsu 211166,China
摘要：The macrophage-mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia.Therefore,macrophage-based therapeutic targets need to be explored for ischemic disease.In the current study,we found that the mRNA levels of scavenger receptor A1(Sr-a1)were elevated in patients with critical limb ischemia,based on an analysis of the Gene Expression Omnibus data.We then investigated the role and underlying mechanisms of macrophage SR-A1 in a mouse hindlimb ischemia(HLI)model.Compared with the Sr-a1fl/fl mice,the LyzCre/+/Sr-a1flox/flox(Sr-a1ΔMΦ)mice showed significantly reduced laser Doppler blood flow in the ischemic limb on day seven after HLI.Consistently,histological analysis revealed that the ischemic limb of the Sr-a1ΔMΦ mice exhibited more severe and prolonged necrotic morphology,inflammation,fibrosis,decreased vessel density,and delayed regeneration than that of the control Sr-a1fl/fl mice.Furthermore,restoring wild-type myeloid cells to the Sr-a1 knockout mice effectively improved the Doppler perfusion in the ischemic limb and mitigated skeletal muscle damage seven days after HLI.Consistent with these in vivo findings,co-cultivating macrophages with the mouse myoblast cell line C2C12 revealed that the Sr-a1-/-bone marrow macrophages significantly inhibited myoblast differentiation in vitro.Mechanistically,SR-A1 enhanced the skeletal muscle regeneration in response to HLI by inhibiting oncostatin M production via suppression of the NF-κB signaling activation.These findings indicate that SR-A1 may be a promising candidate protein to improve tissue repair and regeneration in peripheral ischemic arterial disease.
机标关键词：regenerationreceptorischemiaafterhindlimbmacrophagemusclepromotes
分类号：R543(心脏、血管（循环系）疾病)
论文发表日期：2025-01-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：14( 中插2,23-35 )
英文信息