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

Abstract

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.

• Authors: Jeong-Han Kang, Hyun-Ji Cho, In-Seon Lee, Moonkyu Kim, In-Kyu Lee, Young-Chae Chang
• Journal: Proteomics (Proteomics) Vol. 9 Issue 19 Pg. 4445-56 (Oct 2009) ISSN: 1615-9861 [Electronic] Germany
• PMID: 19688726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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