Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis

Cell Physiol Biochem. 2017;42(6):2441-2452. doi: 10.1159/000480198. Epub 2017 Aug 21.

Abstract

Background/aims: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB-induced mesangial cell proliferation in vitro.

Methods: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed.

Results: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB- stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB-stimulated cells.

Conclusion: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB-stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.

Keywords: Huaier; Mesangial proliferative glomerulonephritis; Mxi-1; Thy-1 nephritis.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Becaplermin
  • CDC2 Protein Kinase / metabolism
  • Cell Proliferation / drug effects*
  • Complex Mixtures / pharmacology*
  • Cyclin B1 / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Isoantibodies / metabolism*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Glomerulus / cytology
  • Male
  • Mesangial Cells / cytology
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Nephritis / metabolism
  • Nephritis / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-sis / pharmacology
  • Rats
  • Rats, Wistar
  • Trametes
  • Tumor Suppressor Proteins / metabolism
  • Up-Regulation / drug effects

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Complex Mixtures
  • Cyclin B1
  • Drugs, Chinese Herbal
  • Isoantibodies
  • Mxi1 protein, rat
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-sis
  • Tumor Suppressor Proteins
  • anti-Thy antibody
  • huaier
  • Becaplermin
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinase 2