title: Biological responses to PDGF-AA versus PDGF-CC in renal fibroblasts.
abstract: BACKGROUND
  Platelet-derived growth factors (PDGF)-AA and -CC mediate renal fibroblast proliferation and/or renal fibrosis. Whereas PDGF-CC binds to both the PDGF receptors (PDGFRs)-αα- and -αβ, PDGF-AA binds more selectively to the αα-receptor, suggesting potential differences in the biological activities.
  
  
  METHODS
  We compared signal transduction, gene expression as well as changes in the proteome induced by PDGF-AA and -CC in rat renal fibroblasts, which express both PDGFR subunits. The growth factor concentrations used were chosen based on their equipotency in inducing rat renal fibroblast proliferation.
  
  
  RESULTS
  Both PDGF-AA and PDGF-CC induced phosphorylation and activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2. Renal fibroblast proliferation induced by either PDGF-AA or -CC could be blocked by signal transduction inhibitors of the mitogen-activated protein kinase (MAPK)-, Janus-kinase (JAK)/signal transducers and activators of transcription (STAT) and phosphatidyl-inositol-3-kinase (PI3K) pathway, pointing to the involvement of all the three pathways. However, quantitative differences between both the stimulations were minor. Additive or synergistic effects by stimulating simultaneously with PDGF-AA and -CC were not observed. Using a proteomic approach we found eleven differentially expressed proteins, which were quantitatively altered after treatment with either PDGF-AA or PDGF-CC. The regulation of calreticulin and inorganic pyrophosphatase 1 could be verified by western blotting.
  
  
  CONCLUSIONS
  PDGF-AA and -CC exhibit almost identical biological effects on signal transduction and proteome in cultured renal fibroblasts, suggesting that the ligands exert their activity essentially through the commonly bound PDGFR-αα. Nonetheless, two differentially expressed proteins were identified which might be involved in the development of renal failure.
authors.affiliation: Division of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Seikrit
authors.forename: Corinna
authors.initials: C
authors.lastname: Henkel
authors.forename: Claudia R C
authors.initials: CR
authors.lastname: van Roeyen
authors.forename: Dirk
authors.initials: D
authors.lastname: Bokemeyer
authors.forename: Frank
authors.initials: F
authors.lastname: Eitner
authors.forename: Ina V
authors.initials: IV
authors.lastname: Martin
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Müller-Newen
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D024202:Electrophoretic Mobility Shift Assay; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; C411423:platelet-derived growth factor C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3