Abstract
Hypertrophic scar is an unavoidable result of wound healing following burns and trauma, which remains a challenging problem for clinicians. Previously, we demonstrated that exosomal microRNAs (miRs) of human amniotic epithelial cells accelerated wound healing and inhibited scar formation. However, the underlying mechanism is still unclear. In this particular study, we found that miR-let-7d reduced collagen deposition, and this was accompanied by decreased level of iron content in myofibroblasts. Importantly, inhibition of miR-let-7d in myofibroblasts accelerated collagen deposition and promoted cell proliferation. In addition, bioinformatics prediction combined with classical dual-luciferase reporter gene assay demonstrated that the cellular iron importer divalent metal transporter 1 (DMT1) was a target gene of miR-let-7d, and the miR-let-7d mimics inhibited the expression of DMT1 in myofibroblasts. Moreover, silencing of DMT1 with small interfering RNA (siRNA) reduced the deposition of extracellular matrix. Consistent with the results in vitro, the miR-let-7d mimics effectively ameliorated hypertrophic scar fibrosis in a rabbit ear hypertrophic scar model. Taken together, our results indicated for the first time that miR-let-7d attenuated hypertrophic scar fibrosis through modulation of iron metabolism by reducing iron uptake through DMT1, which may provide a novel therapeutic strategy for hypertrophic scar.
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Data availability
The data used to support the findings of this study are available from the corresponding author upon request.
Abbreviations
- Col-I:
-
Collagen I
- Col-III:
-
Collagen III
- DMT1:
-
Divalent metal transporter 1
- FTH1:
-
Ferritin heavy chain 1
- FPN1:
-
Ferroportin 1
- miRs:
-
MicroRNAs
- NC:
-
Negative control
- PBS:
-
Phosphate buffer saline
- siRNA:
-
Small interfering RNA
- TFR1:
-
Transferrin receptor 1
- α-SMA:
-
Alpha-smooth muscle actin
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81901964) and the Booster Plan of Xijing Hospital (XJZT18MJ10).
Funding
This work was supported by the National Natural Science Foundation of China (81901964) and the Booster Plan of Xijing Hospital (XJZT18MJ10).
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Zhao, B., Shi, X., Feng, D. et al. MicroRNA let-7d attenuates hypertrophic scar fibrosis through modulation of iron metabolism by reducing DMT1 expression. J Mol Histol 54, 77–87 (2023). https://doi.org/10.1007/s10735-023-10113-0
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DOI: https://doi.org/10.1007/s10735-023-10113-0