Journal
PROTEOMICS
Volume 9, Issue 19, Pages 4445-4456Publisher
WILEY
DOI: 10.1002/pmic.200800941
Keywords
2-DE; Cell biology; Fibrosis; Plasminogen activator inhibitor-1
Funding
- Korean Mintstry of Education, Science and Technology, Republic of Korea
- Korean Government [KRF-2008-313-C00628]
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Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 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-beta 1-induced fibrosis processes, we performed a proteomic analysis of TGF-beta 1-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.
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