Comparative proteome analysis of TGF-beta1-induced fibrosis processes in normal rat kidney interstitial fibroblast cells in response to ascofuranone.
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.
Kang
Jeong-Han
JH
Department of Pathology, Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine, Daegu 705-034, Korea.
Cho
Hyun-Ji
HJ
Lee
In-Seon
IS
Kim
Moonkyu
M
Lee
In-Kyu
IK
Chang
Young-Chae
YC
D000818:Animals; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D051381:Rats; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D020543:Proteome; D012717:Sesquiterpenes; D053773:Transforming Growth Factor beta1; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C006640:ascofuranone