Open Access

Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway

  • Authors:
    • Bin Zhao
    • Hao Guan
    • Jia-Qi Liu
    • Zhao Zheng
    • Qin Zhou
    • Jian Zhang
    • Lin-Lin Su
    • Da-Hai Hu
  • View Affiliations

  • Published online on: December 1, 2016     https://doi.org/10.3892/ijmm.2016.2816
  • Pages:153-159
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring. The aim of this study was to investigate whether hypoxia drives the transition of dermal fibroblasts to myofibroblasts and to clarify the potential transduction mechanisms involved. First, we observed that keloids are a relatively hypoxic tissue. Second, we found that hypoxia drives the transition of normal dermal fibroblasts to a myofibroblast-like phenotype [high expression of α-smooth muscle actin (α-SMA) and collagen I and III]. Finally, hypoxia effectively facilitated the nuclear import of the Smad2 and Smad3 complex, while blockade with the Smad3 inhibitor, SIS3, significantly impaired the expression of hypoxia-induced fibrosis-related molecules. Taken together, to the best of our knowledge, this study demonstrates for the first time that hypoxia facilitates the transition of dermal fibroblasts to myofibroblasts through the activation of the TGF-β1/Smad3 signaling pathway and our findings may provide a potential target for the treatment of keloids.

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January 2017
Volume 39 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
(total number of cites)

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Copy and paste a formatted citation
APA
Zhao, B., Guan, H., Liu, J., Zheng, Z., Zhou, Q., Zhang, J. ... Hu, D. (2017). Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway. International Journal of Molecular Medicine, 39, 153-159. https://doi.org/10.3892/ijmm.2016.2816
MLA
Zhao, B., Guan, H., Liu, J., Zheng, Z., Zhou, Q., Zhang, J., Su, L., Hu, D."Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway". International Journal of Molecular Medicine 39.1 (2017): 153-159.
Chicago
Zhao, B., Guan, H., Liu, J., Zheng, Z., Zhou, Q., Zhang, J., Su, L., Hu, D."Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway". International Journal of Molecular Medicine 39, no. 1 (2017): 153-159. https://doi.org/10.3892/ijmm.2016.2816