2. Academic Validation
  3. Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis

Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis

  • Adv Sci (Weinh). 2024 Apr 19:e2307238. doi: 10.1002/advs.202307238.
Gaoxiang Yu 1 2 3,  Yijie Chen 4,  Ningning Yang 1 2 3,  Haojie Zhang 1 2 3,  Xuzi Zhang 1 2 3,  Yibo Geng 1 2 3,  Jiayi Zhao 3,  Zhuliu Chen 1 2 3,  Chengji Dong 1 2 3,  Lidan Lin 2 5,  Jianjun Qi 6,  Xuanlong Zhang 2 7,  Xiaoqiong Jiang 2,  Weiyang Gao 1 2 3,  Yuepiao Cai 7,  Xiangyang Wang 1 2 3,  Jian Ding 1 2 3,  Jian Xiao 7,  Kailiang Zhou 1 2 3
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, 325027, China.
  • 3 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, China.
  • 4 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
  • 5 School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, 325035, China.
  • 6 Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, China.
  • 7 Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, China.
PMID: 38639443 DOI: 10.1002/advs.202307238
Abstract

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of Apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic FLAP survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic FLAP survival in endothelial cells and macrophages by inhibiting Ferroptosis via the Keap1-Nrf2 axis. Furthermore, MicroRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited Ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic FLAP survival. These results provide a potential therapeutic strategy to promote ischaemic FLAP survival by administering ABs.

Keywords

KEAP1‐Nrf2; apoptotic bodies; ferroptosis; ischaemic flaps; miR‐339‐5p.

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