Apigenin inhibits fibrous scar formation after acute spinal cord injury through TGFβ/SMADs signaling pathway

  • CNS Neurosci Ther. 2022 Nov;28(11):1883-1894. doi: 10.1111/cns.13929.
Zhengxin Jin  1 Lige Tian  2 Ying Zhang  1 Xiaodi Zhang  3 Jianning Kang  1 Hui Dong  4 Nana Huang  1 Liuzhu Pan  1 Bin Ning  1  4
Affiliations
  • 1. Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
  • 2. Tianjin Medical University, Tianjin, China.
  • 3. School of Clinical Medicine, Weifang Medical University, Weifang, China.
  • 4. Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Abstract

Aim: To investigate the effect of apigenin on fibrous scar formation after mouse spinal cord injury (SCI).

Methods: The pneumatic impactor strike method was used to establish an SCI model. Mice were intraperitoneally injected with 5 mg/kg or 20 mg/kg apigenin daily for 28 days after SCI. The Basso Mouse Scale (BMS) score, hematoxylin-eosin staining, and immunohistochemical staining were used to assess the effect of apigenin on scar formation and motor function recovery. Western blotting and qRT-PCR were used to detect the expression of fibrosis-related parameters in spinal cord tissue homogenates. NIH-3 T3 cells and mouse primary spinal cord fibroblasts, α-Smooth muscle actin (α-SMA), Collagen 1, and fibronectin were used to evaluate apigenin's effect in vitro. Western blotting and immunofluorescence techniques were used to study the effect of apigenin on TGFβ/SMADs signaling.

Results: Apigenin inhibited fibrous scar formation in the mouse spinal cord and promoted the recovery of motor function. It reduced the expression of fibroblast-related parameters and increased the content of nerve growth factor in vivo, decreasing myofibroblast activation and Collagen fiber formation by inhibiting TGFβ-induced SMAD2/3 phosphorylation and nuclear translocation in vitro.

Conclusion: Apigenin inhibits fibrous scar formation after SCI by decreasing fibrosis-related factor expression through TGFβ/SMADs signaling.

Keywords
TGFβ/SMADs; apigenin; fibrous scar; spinal cord injury.
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