Comparative proteome analysis of TGF-beta1-induced fibrosis processes in normal rat kidney interstitial fibroblast cells in response to ascofuranone

Proteomics. 2009 Oct;9(19):4445-56. doi: 10.1002/pmic.200800941.


Transforming growth factor-beta1 (TGF-beta1) has a wide range of biological functions such as the regulation of cell growth, differentiation, and immunological response in various types of cells. Particularly, TGF-beta1 induces plasminogen activator inhibitor-1 (PAI-1) as a major target protein. PAI-1 is associated with fibrosis, thrombosis, and metabolic disorders. In this study, to identify proteins potentially involved in TGF-beta1-induced fibrosis processes, we performed a proteomic analysis of TGF-beta1-induced normal rat kidney cells exposed to ascofuranone (AF). In these cells, we detected 1500 proteins, with 74 differentially expressed proteins identified by MALDI-TOF and reference to the NCBI and Swiss-Prot databases, including PAI-1, peroxisome prdifesator-activated receptor, prohibitin, glutamate formyltransferase, LIM domain protein 1, LASP-1, porphobilinogen deaminase, and peroxiredoxin 2. We also found that AF suppresses expression of profibrotic factors induced by TGF-beta in renal fibroblasts, including matrix proteins and PAI-1. AF was also shown to inhibit selectively phosphorylation of epidermal growth factor receptor, and downstream kinases such as extracellular signal-regulated kinase 1/2 (ERK-1/2). Further ongoing analysis of fibrosis-related proteins will determine AF's potential for application in fibrotic diseases and therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme Inhibitors / metabolism
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblasts* / drug effects
  • Fibroblasts* / metabolism
  • Fibroblasts* / pathology
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Kidney* / cytology
  • Kidney* / drug effects
  • Kidney* / pathology
  • MAP Kinase Kinase Kinases / metabolism
  • Molecular Sequence Data
  • Molecular Structure
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Proteome / analysis*
  • Rats
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / physiology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*


  • Enzyme Inhibitors
  • Plasminogen Activator Inhibitor 1
  • Proteome
  • Sesquiterpenes
  • Transforming Growth Factor beta1
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases
  • ascofuranone