Protective Effect of Low-Molecular-Weight Fucoidan on Radiation-Induced Fibrosis Through TGF-β1/Smad Pathway-Mediated Inhibition of Collagen I Accumulation

Mar Drugs. 2020 Feb 27;18(3):136. doi: 10.3390/md18030136.


Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-β1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-β1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF.

Keywords: Smad pathway; TGF-β1; collagen I; low-molecular-weight fucoidan; radiation-induced fibrosis.

MeSH terms

  • Animals
  • Collagen / metabolism
  • Mice
  • NIH 3T3 Cells / drug effects
  • Polysaccharides / pharmacology*
  • Protective Agents / pharmacology*
  • Radiation Pneumonitis / prevention & control*
  • Signal Transduction
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / metabolism


  • Polysaccharides
  • Protective Agents
  • Smad3 Protein
  • Transforming Growth Factor beta
  • Collagen
  • fucoidan