Heat shock protein 47 as indispensible participant in liver fibrosis: Possible protective effect of lactoferrin

IUBMB Life. 2018 Aug;70(8):795-805. doi: 10.1002/iub.1884. Epub 2018 Aug 9.


Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)-induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA-treated), LF (LF + TAA-treated), and SM (SM + TAA-treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor-beta 1, matrix metalloproteinase-2, 8-hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795-805, 2018.

Keywords: HSP47; lactoferrin; liver fibrosis; silymarin; thioacetamide.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Gene Expression Regulation / drug effects
  • HSP47 Heat-Shock Proteins / antagonists & inhibitors
  • HSP47 Heat-Shock Proteins / genetics*
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Humans
  • Lactoferrin / administration & dosage*
  • Liver / drug effects*
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Matrix Metalloproteinase 2 / genetics
  • Rats
  • Silymarin / administration & dosage
  • Thioacetamide / administration & dosage
  • Transforming Growth Factor beta1 / genetics


  • Antioxidants
  • HSP47 Heat-Shock Proteins
  • Silymarin
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Thioacetamide
  • Lactoferrin
  • Matrix Metalloproteinase 2