cyclin-d1 has been researched along with Cicatrix--Hypertrophic* in 1 studies
1 other study(ies) available for cyclin-d1 and Cicatrix--Hypertrophic
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The IL-6 trans-signaling-STAT3 pathway mediates ECM and cellular proliferation in fibroblasts from hypertrophic scar.
The molecular mechanisms behind the pathogenesis of postburn hypertrophic scar (HS) remain unclear. Here, we investigate the role of the IL-6 trans-signaling-signal transducer and activator of transcription (STAT)3 pathway in HS fibroblasts (HSFs) derived from post-burn HS skin. HSF showed increased Tyr 705 STAT3 phosphorylation compared with normal fibroblast (NF) after IL-6•IL-6Rα stimulation by immunoassays. The endogenous STAT3 target gene, SOCS3, was upregulated in HSFs and showed increased STAT3 binding on its promoter relative to NFs in a chromatin immunoprecipitation assay. We observed that the cell-surface signaling transducer glycoprotein 130 is upregulated in HSFs by quantitative real-time reverse-transcriptase-PCR and flow cytometry. The production of excessive extracellular matrix (ECM), including the expression of alpha2 (1) procollagen (Col1A2) and fibronectin 1 (FN), was seen in HSFs. A STAT3 peptide inhibitor abrogated FN and Col1A2 gene expression in HSFs indicating involvement of STAT3 in ECM production. The cellular proliferation markers Cyclin D1, Bcl-Xl, and c-Myc were also upregulated in HSF, and knockdown of STAT3 by small interfering RNA attenuated c-Myc expression indicating the essential role of STAT3 in fibroblast proliferation. Taken together, our results suggest that the IL-6 trans-signaling-STAT3 pathway may have an integral role in HS pathogenesis, and disruption of this pathway could be a potential therapeutic strategy for the treatment of post-burn HS. Topics: bcl-X Protein; Cell Proliferation; Cicatrix, Hypertrophic; Collagen Type I; Cyclin D1; Extracellular Matrix; Fibroblasts; Fibronectins; Glycoproteins; Humans; Interleukin-6; Proto-Oncogene Proteins c-myc; Signal Transduction; STAT3 Transcription Factor; Up-Regulation | 2013 |