Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis

Sen Ren, Jing Chen, Jiahe Guo, Yutian Liu, Hewei Xiong, Boping Jing, Xiaofan Yang, Gongchi Li, Yu Kang, Cheng Wang, Xiang Xu, Zhenyu Liu, Maojie Zhang, Kaituo Xiang, Chengcheng Li, Qianyun Li, Hans Günther Machens, Zhenbing Chen

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes from adipose-derived stem cells (ADSC-EXOs) promote diabetic wound healing through the modulation of oxidative stress. We found that ADSC-EXOs could promote proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, and endothelial cells. Furthermore, ADSC-EXOs reduced the reactive oxygen species (ROS) levels in these cells and protected them against hypoxic and oxidative stress damage. Finally, the local injection of ADSC-EXOs at wound sites significantly increased collagen deposition and neovascularization while reducing ROS levels and cell death; thus, it led to accelerated diabetic wound closure. The mechanism underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on the cell surface; these functions could be inhibited by an anti-HSP90 antibody. Exosomal HSP90 could bind to the low-density lipoprotein receptor-related protein 1 (LRP1) receptor on the recipient cell membrane, leading to activation of the downstream AKT signaling pathway. Knockdown of LRP1 and inhibition of the AKT signaling pathway by LY294002 in fibroblasts was sufficient to impair the beneficial effect of ADSC-EXOs. In summary, ADSC-EXOs significantly accelerated diabetic wound closure through an exosomal HSP90/LRP1/AKT signaling pathway.

Original languageEnglish
Article number3229
JournalCells
Volume11
Issue number20
DOIs
StatePublished - Oct 2022

Keywords

  • adipose-derived stem cell
  • diabetic wound
  • exosomes
  • heat shock protein 90
  • oxidative stress

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