PMID- 37303686
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230613
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 15
IP  - 5
DP  - 2023
TI  - Metformin induces M2 polarization via AMPK/PGC-1alpha/PPAR-gamma pathway to improve 
      peripheral nerve regeneration.
PG  - 3778-3792
AB  - OBJECTIVES: Investigating the effect of metformin on peripheral nerve 
      regeneration and the molecular mechanism. METHODS: In this study, a rat model of 
      sciatic nerve injury and an inflammatory bone marrow-derived macrophage (BMDM) 
      cell model were established. We assessed the sensory and motor function of the 
      hind limbs four weeks after sciatic nerve injury, immunofluorescence was used to 
      detect axonal regeneration and myelin formation, as well as local macrophage 
      subtypes. We investigated the polarizing effect of metformin on inflammatory 
      macrophages, and western blotting was applied to detect the molecular mechanisms 
      behind it. RESULTS: Metformin treatment accelerated functional recovery, axon 
      regeneration and remyelination, and promoted M2 macrophage polarization. In vivo, 
      metformin transformed pro-inflammatory macrophages into pro-regeneration M2 
      macrophages. Protein expression levels of phosphorylated AMP-activated protein 
      kinase (p-AMPK), proliferator-activated receptor-gamma co-activator 1alpha (PGC-1alpha), and 
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) increased upon metformin 
      treatment. Moreover, inhibition of AMPK abolished the effects of metformin 
      treatment on M2 polarization. CONCLUSION: Metformin promoted M2 macrophage 
      polarization by activating the AMPK/PGC-1alpha/PPAR-gamma signaling axis, thereby 
      promoting peripheral nerve regeneration.
CI  - AJTR Copyright (c) 2023.
FAU - Zhou, Zekun
AU  - Zhou Z
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
FAU - Luo, Gaojie
AU  - Luo G
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
FAU - Li, Cheng
AU  - Li C
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
FAU - Zhang, Peiyao
AU  - Zhang P
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
FAU - Li, Xiaoxiao
AU  - Li X
AD  - Department of Pathology, Changsha Medical University Changsha, Hunan, China.
FAU - Tang, Juyu
AU  - Tang J
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
FAU - Qing, Liming
AU  - Qing L
AD  - Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central 
      South University Changsha, Hunan, China.
LA  - eng
PT  - Journal Article
DEP - 20230515
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC10250979
OTO - NOTNLM
OT  - AMPK/PGC-1alpha/PPAR-gamma signaling axis
OT  - Metformin
OT  - macrophage polarization
OT  - peripheral nerve regeneration
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/06/12 06:42
MHDA- 2023/06/12 06:43
PMCR- 2023/05/15
CRDT- 2023/06/12 03:56
PHST- 2023/03/26 00:00 [received]
PHST- 2023/05/04 00:00 [accepted]
PHST- 2023/06/12 06:43 [medline]
PHST- 2023/06/12 06:42 [pubmed]
PHST- 2023/06/12 03:56 [entrez]
PHST- 2023/05/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2023 May 15;15(5):3778-3792. eCollection 2023.