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.
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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
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This work was supported by National Natural Science Foundation of China (81601693, 81372069, 81703924).
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Wu, X., Li, J., Yang, X. et al. miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF-1α via PI3K/AKT pathway. J Mol Hist 49, 377–387 (2018). https://doi.org/10.1007/s10735-018-9778-z
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DOI: https://doi.org/10.1007/s10735-018-9778-z