1. Academic Validation
  2. Metformin attenuates post-epidural fibrosis by inhibiting the TGF-β1/Smad3 and HMGB1/TLR4 signaling pathways

Metformin attenuates post-epidural fibrosis by inhibiting the TGF-β1/Smad3 and HMGB1/TLR4 signaling pathways

  • J Cell Mol Med. 2021 Apr;25(7):3272-3283. doi: 10.1111/jcmm.16398.
Zeyuan Song 1 2 Tao Wu 1 Jinpeng Sun 1 Haoran Wang 1 Feng Hua 1 Yap San Min Nicolas 1 Rupesh Kc 1 Kun Chen 1 Zhen Jin 1 Jun Liu 1 Mingshun Zhang 3
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Department of Emergence Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
  • 3 NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, China.
Abstract

Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-β1/SMAD3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy.

Keywords

HMGB1; TGF-β1; epidural fibrosis; metabolomics; metformin; spine operation.

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