Suppressor of cytokine signaling 3 negative regulation of signal transducer and activator of transcription 3 in platelet-derived growth factor-induced fibroblast migration

• Published in: Journal of dermatology 2007-08, Vol.34 (8), p.523-530
• Main Authors: NAGAI, Hiroshi, TOKUMARU, Sho, SAYAMA, Koji, SHIRAKATA, Yuji, HANAKAWA, Yasushi, HIRAKAWA, Satoshi, DAI, Xiuju, TOHYAMA, Mikiko, YANG, Lujun, HASHIMOTO, Koji
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Blotting, Western; Cell Movement - physiology; Cells, Cultured; fibroblasts; Fibroblasts - enzymology; Fibroblasts - physiology; Genetic Vectors; Humans; migration; Mutation; Phosphorylation; platelet-derived growth factor (PDGF); Platelet-Derived Growth Factor - physiology; Polymerase Chain Reaction; signal transducer and activator of transcription 3 (STAT3); Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - physiology; suppressor of cytokine signaling 3 (SOCS3); Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - physiology; Transfection; Wound Healing - physiology
• ISSN: 0385-2407; 1346-8138
• DOI: 10.1111/j.1346-8138.2007.00325.x

ABSTRACT 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.