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Αλέξανδρος Γ. Σφακιανάκης

Tuesday, March 9, 2021

MicroRNA-497-5p downregulation inhibits cell viability, reduces extracellular matrix deposition and induces apoptosis in human hyperplastic scar fibroblasts by regulating Smad7

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Exp Ther Med. 2021 Apr;21(4):384. doi: 10.3892/etm.2021.9815. Epub 2021 Feb 23.

ABSTRACT

Hypertrophic scars (HSs) are characterized by excessive extracellular matrix deposition and excessive growth of dense fibrous tissues. MicroRNAs (miRNAs/miRs) serve key roles in HS formation. The present study investigated the expression, role and mechanism underlying the effects of miR-497-5p in HS formation. miR-497-5p expression was detected via reverse transcription-quantitative PCR. The association between miR-497-5p and Smad7 was analyzed using TargetScan and luciferase reporter assays. Protein expression levels of extracellular matrix markers were measured via western blotting. Cell viability and apoptosis were determined using the Cell Counting Kit-8 assay and flow cytometry, respectively. The results suggested that miR-497-5p expression was upregulated in HS tissues and human HS fibroblasts (hHSFs) compared with healthy control skin tissue s and CCC-ESF-1 cells, respectively. Smad7 was directly targeted by miR-497-5p, and was downregulated in HS tissues and hHSFs compared with healthy control skin tissues and CCC-ESF-1 cells, respectively. Moreover, Smad7 upregulation significantly inhibited cell viability, decreased extracellular matrix deposition and induced apoptosis in hHSFs compared with the control-plasmid group. Moreover, the results indicated that, compared with the inhibitor control group, miR-497-5p inhibitor inhibited cell viability, decreased extracellular matrix deposition and induced apoptosis in hHSFs, which were significantly reversed by Smad7 knockdown. In conclusion, the results indicated that miR-497-5p downregulation repressed HS formation by inhibiting extracellular matrix deposition and hHSF proliferation at least partly by targeting Smad7.

PMID:33680106 | PMC:PMC7918061 | DOI:10.3892/etm.2021.9815

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