Open AccessMetformin attenuates post‐epidural fibrosis by inhibiting the TGF‐β1/Smad3 and HMGB1/TLR4 signaling pathways
Author(s) -
Song Zeyuan,
Wu Tao,
Sun Jinpeng,
Wang Haoran,
Hua Feng,
Nicolas Yap San Min,
KC Rupesh,
Chen Kun,
Jin Zhen,
Liu Jun,
Zhang Mingshun
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16398
Subject(s) - metformin , fibrosis , medicine , fibronectin , fibroblast , hmgb1 , laminectomy , pharmacology , diabetes mellitus , endocrinology , inflammation , extracellular matrix , spinal cord , biology , cell culture , microbiology and biotechnology , genetics , psychiatry
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.