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Journal of Molecular Histology

, Volume 49, Issue 4, pp 377–387 | Cite as

miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF-1α via PI3K/AKT pathway

  • Xue Wu
  • Jun Li
  • Xuekang Yang
  • Xiaozhi Bai
  • Jihong Shi
  • Jianxin Gao
  • Yan Li
  • Shichao Han
  • Yijie Zhang
  • Fu Han
  • Yang Liu
  • Xiaoqiang Li
  • Kejia Wang
  • Julei Zhang
  • Zheng Wang
  • Ke Tao
  • Dahai Hu
Original Paper

Abstract

Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by the excessive proliferation of fibroblasts and often considered as a kind of benign skin tumor. microRNA-155 (miR-155) is usually served as a promising marker in antitumor therapy. In view of the similarities of hypertrophic scar and tumor, it is predicted that miR-155 may be a novel therapeutic target in clinical trials. Here we found the expression levels of miR-155 was gradually down regulated and HIF-1α was upregulated in HS tissue and HS derived fibroblasts (HFs). And cell proliferation was inhibited when miR-155 was overexpressed or HIF-1α was silenced. Moreover, overexpression of miR-155 in HFs could reduce the expression of collagens in vitro and inhibit the collagen fibers arrangement in vivo, whereas miR-155 knockdown gave opposite results. Furthermore, we found that miR-155 directly targeted the HIF-1α, which could also independently inhibit the expression of collagens in vitro and obviously improved the appearance and architecture of the rabbit ear scar in vivo when it was silencing. Finally, we found that PI3K/AKT pathway was enrolled in these processes. Together, our results indicated that miR-155 was a critical regulator in the formation and development of hypertrophic scar and might be a potential molecular target for hypertrophic scar therapy.

Keywords

miR-155 Hypoxia inducible factor-1α Hypertrophic scar AKT pathway Fibroblast 

Abbreviations

HS

Hypertrophic scar

HFs

Hypertrophic scar derived fibroblasts

NS

Normal skin

NSFs

Normal skin derived fibroblasts

HIF1α

Hypoxia inducible factor1α

Col I

Collagen I

Col III

Collagen III

a-SMA

a-smooth muscle actin

Notes

Funding

This work was supported by National Natural Science Foundation of China (81601693, 81372069, 81703924).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10735_2018_9778_MOESM1_ESM.docx (474 kb)
Supplementary material 1 (DOCX 473 KB)

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Xue Wu
    • 1
    • 2
  • Jun Li
    • 1
  • Xuekang Yang
    • 1
  • Xiaozhi Bai
    • 1
  • Jihong Shi
    • 1
  • Jianxin Gao
    • 1
  • Yan Li
    • 1
  • Shichao Han
    • 1
  • Yijie Zhang
    • 1
  • Fu Han
    • 1
  • Yang Liu
    • 1
  • Xiaoqiang Li
    • 1
  • Kejia Wang
    • 1
  • Julei Zhang
    • 1
  • Zheng Wang
    • 2
  • Ke Tao
    • 1
  • Dahai Hu
    • 1
  1. 1.Department of Burns and Cutaneous Surgery, Xijing HospitalThe Fourth Military Medical UniversityXi’anChina
  2. 2.Shaanxi Collaborative Innovation Center of Chinese Medicinal ResourcesShaanxi University of Chinese MedicineXi’anChina

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