TGF-β/Smad and JAK/STAT pathways are involved in the anti-fibrotic effects of propylene glycol alginate sodium sulphate on hepatic fibrosis

J Cell Mol Med. 2020 May;24(9):5224-5237. doi: 10.1111/jcmm.15175. Epub 2020 Mar 31.

Abstract

Liver fibrosis, a consequence of unhealthy modern lifestyles, has a growing impact on human health, particularly in developed countries. Here, we have explored the anti-fibrotic effects of propylene glycol alginate sodium sulphate (PSS), a natural extract from brown algae, in fibrotic mice and cell models. Thus, we established bile duct ligature and carbon tetrachloride mouse models and LX-2 cell models with or without PSS treatment. Liver pathological sections and the relevant indicators in serum and liver tissues were examined. PSS prevented hepatic injury and fibrosis to a significant extent, and induced up-regulation of matrix metalloproteinase-2 and down-regulation of tissue inhibitor of metalloproteinase-1 through suppressing the transforming growth factor β1 (TGF-β1)/Smad pathway. PSS additionally exerted an anti-autophagy effect through suppressing the Janus kinase (JAK) 2/transducer and activator of transcription 3 (STAT3) pathway. In conclusion, PSS prevents hepatic fibrosis by suppressing inflammation, promoting extracellular matrix (ECM) decomposition and inactivating hepatic stellate cells through mechanisms involving the TGF-β1/Smad2/3 and JAK2/STAT3 pathways in vivo and in vitro.

Keywords: JAK2/STAT3; TGF-β1/Smad2/3; autophagy; liver fibrosis; propylene glycol alginate sodium sulphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / pharmacology
  • Alginates / therapeutic use*
  • Animals
  • Autophagy / drug effects
  • Bile Ducts / pathology
  • Carbon Tetrachloride
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Janus Kinases / metabolism*
  • Ligation
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Mice, Inbred C57BL
  • Models, Biological
  • STAT Transcription Factors / metabolism*
  • Signal Transduction*
  • Smad Proteins / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation / drug effects

Substances

  • Alginates
  • STAT Transcription Factors
  • Smad Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta
  • propylene glycol alginate sodium sulfate
  • Carbon Tetrachloride
  • Janus Kinases
  • Matrix Metalloproteinase 2