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Stat3 contributes to keloid pathogenesis via promoting collagen production, cell proliferation and migration

Oncogene volume 25, pages 5416–5425 (2006)Cite this article

Abstract

Keloids, partially considered as benign tumors, represent the most extreme example of cutaneous scarring that uniquely afflicts humans as a pathological response to wound healing. It is characterized by excessive deposition of collagen and other extracellular matrix components by dermal fibroblasts. Upon cutaneous injury, cocktails of chemokines, cytokines and growth factors are secreted temporally and spatially to direct appropriate responses from neutrophils, macrophages, keratinocytes and fibroblasts to facilitate normal wound healing. Signal transducer and activator of transcription 3 (Stat3) is an oncogene and a latent transcription factor activated by various cytokines and growth factors. We investigated the possible role of Stat3 in keloid scar pathogenesis by examining skin tissue and cultured fibroblasts from keloid-scarred patients. We observed enhanced expression and phosphorylation of Stat3 in keloid scar tissue, and in cultured keloid fibroblasts (KFs) in vitro. Increased activation of Janus kinase (Jak)2, but not Jak1, was detected in KFs, and suppression of Jak2 by its inhibitor repressed Stat3 Y705 phosphorylation. Inhibition of Stat3 expression and phosphorylation by short interfering RNA or Cucurbitacin I resulted in the loss of collagen production, impaired proliferation and delayed cell migration in KFs. We show, for the first time, a role of Stat3 in keloid pathogenesis. Inhibitors of Stat3 may be useful therapeutic strategies for the prospective treatment of keloid scars.

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Acknowledgements

We are grateful to Dr Garry Nolan for the retroviral Phoenix packaging cell line. We thank Dr Birgit Lane for helpful discussions, Zheng Qi, Guo Ke, Li Jie and Bin Qi from the Histology Unit at the Institute of Molecular and Cell Biology, Singapore, for their kind assistance. The research work at the Institute of Molecular and Cell Biology was supported by the Agency of Science, Technology and Research (A*STAR), Singapore. This research was also supported by A*STAR-Biomedical Research Council (BMRC) grant 02/1/21/19/106 (to Lim IJ and Phan TT). Xinmin Cao is also an adjunct professor at the Department of Biochemistry, National University of Singapore, Singapore.

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Authors and Affiliations

  1. Institute of Molecular and Cell Biology, Proteos, Singapore

    C P Lim & X Cao

  2. Department of Surgery, National University of Singapore, Singapore

    T-T Phan & I J Lim

  3. Department of Bioengineering, National University of Singapore, Singapore

    T-T Phan

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  1. C P Lim
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Correspondence to X Cao.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lim, C., Phan, TT., Lim, I. et al. Stat3 contributes to keloid pathogenesis via promoting collagen production, cell proliferation and migration. Oncogene 25, 5416–5425 (2006). https://doi.org/10.1038/sj.onc.1209531

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