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MicroRNA-192 regulates hypertrophic scar fibrosis by targeting SIP1

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Abstract

Hypertrophic scar (HS) is a fibro-proliferative disorder which is characterized by excessive deposition of collagen and accumulative activity of myofibroblasts. Increasing evidences have demonstrated miRNAs play a pivotal role in the pathogenesis of HS. MiR-192 is closely associated with renal fibrosis, but its effect on HS formation and skin fibrosis remains unknown. In the study, we presented that miR-192 was up-regulated in HS and HS derived fibroblasts (HSFs) compared to normal skin (NS) and NS derived fibroblasts (NSFs), accompanied by the reduction of smad interacting protein 1 (SIP1) expression and the increase of Col1, Col3 and α-SMA levels. Furthermore, we confirmed SIP1 was a direct target of miR-192 by using luciferase reporter assays. Meanwhile, the overexpression of miR-192 increased the levels of Col1, Col3 and α-SMA. The synthesis of collagen and more positive α-SMA staining were also observed in bleomycin-induced dermal fibrosis model of BALB/c mice treated with subcutaneous miR-192 mimics injection, whereas the inhibition of miR-192 decreased the expression of Col1, Col3 and α-SMA. Moreover, SIP1 siRNA could enhance the levels of Col1, Col3 and α-SMA, showing that the effect of knockdown SIP1 was similar to miR-192 mimics, and the phenomenon manifested miR-192 regulated HS fibrosis by targeting SIP1. Together, our results indicated that miR-192 was a critical factor of HS formation and facilitated skin fibrosis by targeting directly SIP1.

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Abbreviations

HS:

Hypertrophic scar

HSFs:

Hypertrophic scar derived fibroblasts

NS:

Normal skin

NSFs:

Normal skin derived fibroblasts

SIP1:

Smad interacting protein 1

ECM:

Extracellular matrix

3′-UTR:

3′-Untranslated regions

α-SMA:

α-smooth muscle actin

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81171811, 81372069, 81571914 and 81272098).

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Authors and Affiliations

  1. Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi’an, 710032, China

    Yan Li, Julei Zhang, Wei Zhang, Yang Liu, Yuehua Li, Kejia Wang, Yijie Zhang, Chen Yang, Xiaoqiang Li, Jihong Shi, Linlin Su & Dahai Hu

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  1. Yan Li
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  2. Julei Zhang
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Correspondence to Dahai Hu.

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Yan Li, Julei Zhang and Wei Zhang are co-first authors.

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Li, Y., Zhang, J., Zhang, W. et al. MicroRNA-192 regulates hypertrophic scar fibrosis by targeting SIP1. J Mol Hist 48, 357–366 (2017). https://doi.org/10.1007/s10735-017-9734-3

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