Suppressor of cytokine signaling 3 negative regulation of signal transducer and activator of transcription 3 in platelet-derived growth factor-induced fibroblast migration.
Platelet-derived growth factor (PDGF) is involved in wound healing, but PDGF-induced fibroblast migration and the intracellular signaling mechanisms of fibroblast migration are poorly understood. Signal transducer and activator of transcription 3 (STAT3) is involved in migration and is negatively regulated by the suppressor of cytokine signaling 3 (SOCS3). We studied the PDGF induction of fibroblast migration in vitro and the involvement of STAT3 and SOCS3. We found that PDGF activated STAT3 and strongly induced fibroblast migration. Transfection with a dominant-negative mutant of STAT3 almost completely abolished PDGF-induced fibroblast migration and STAT3 phosphorylation. Next, we studied the mechanisms that regulate fibroblast migration. PDGF enhanced the expression of SOCS3 by 2.8-fold at 1 h. Transfection with SOCS3 almost completely abolished PDGF-induced STAT3 phosphorylation and reduced fibroblast migration to 47% of control, indicating that SOCS3 acts as a negative regulator of PDGF-induced fibroblast migration. In conclusion, PDGF induces fibroblast migration under the control of STAT3-SOCS3.
Department of Dermatology, Ehime University School of Medicine, Ehime, Japan. hiroshi@m.ehime-u.ac.jp
Hiroshi
H
Nagai
Sho
S
Tokumaru
Koji
K
Sayama
Yuji
Y
Shirakata
Yasushi
Y
Hanakawa
Satoshi
S
Hirakawa
Xiuju
X
Dai
Mikiko
M
Tohyama
Lujun
L
Yang
Koji
K
Hashimoto
D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D016133:Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014945:Wound Healing / Q000502:physiology
D010982:Platelet-Derived Growth Factor; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins