Baicalein inhibits proliferation and collagen synthesis of mice fibroblast cell line NIH/3T3 by regulation of miR-9/insulin-like growth factor-1 axis

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3202-3211. doi: 10.1080/21691401.2019.1645150.

Abstract

The aberrant scar is a challenging problem. Baicalein has effects in attenuating hypertrophic scar formation. Herein, the roles of baicalein in NIH-3T3 were obtained. Cells were treated by baicalein. CCK-8 method and western blot were used to detect cell viability and proliferation-related factors. Furthermore, collagen 1, collagen 3 and α-SMA expression were detected by qRT-PCR and western blot. Besides, total soluble collagen was detected by Sircol assay. In addition, the levels of NF-κB and Wnt/β-catenin signal pathways related factors were determined by western blot. The relationship between miR-9 and insulin-like growth factor (IGF)-1 were tested by luciferase reporter assay, qRT-PCR and western blot. We found baicalein cell restrained proliferation and collagen production. Besides, baicalein increased expression of miR-9 and further experiments validated that transfection with miR-9 inhibitor reversed the results led by baicalein. Moreover, baicalein decreased the phosphorylation of pathway-related proteins while transfection with miR-9 inhibitor revised this result. Otherwise, IGF-1 was authenticated as a target of miR-9 and si-IGF-1 reversed the miR-9 inhibitor-induced change in cell proliferation and collagen production. In conclusion, baicalein restrained cell proliferation and collagen production by regulating miR-9/IGF-1 axis through NF-κB and Wnt/β-catenin signal pathways. Highlights: Baicalein restrains NIH/3T3 cell proliferation and collagen production. Baicalein restrains NF-κB and Wnt/β-catenin signal pathways. IGF-1 is a target of miR-9. Baicalein exerts its functions by regulating miR-9/IGF-1 axis.

Keywords: IGF-1; NF-κB; Scar; baicalein; miR-9; β-catenin.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Collagen / biosynthesis*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Flavanones / pharmacology*
  • Insulin-Like Growth Factor I / genetics*
  • Mice
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • NIH 3T3 Cells
  • Up-Regulation / drug effects
  • Wnt Signaling Pathway / drug effects

Substances

  • Flavanones
  • MIRN9 microRNA, mouse
  • MicroRNAs
  • NF-kappa B
  • baicalein
  • Insulin-Like Growth Factor I
  • Collagen