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Updated: Oct 17, 2025

In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding
Published on: May 1, 2020
MicroRNA-18a-5p represses scar fibroblast proliferation and extracellular matrix deposition through regulating Smad2
Tianshi Li1, Yiguang Wu2, Dandan Liu1
1Department of Plastic and Cosmetic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Abstract:
The aim of the present study was to investigate the expression and role of microRNA-18a-5p (miR-18a-5p) during the formation of hypertrophic scar (HS), and to further explore the molecular mechanisms involved. Downregulation of miR-18a-5p in HS tissues and human HS fibroblasts (hHSFs) was detected by reverse transcription-quantitative polymerase chain reaction. The binding sites between miR-18a-5p and the 3'-untranslated region of SMAD family member 2 (Smad2) were predicted by TargetScan and confirmed by dual-luciferase reporter assay. To investigate the role of miR-18a-5p in HS formation, the effects of miR-18a-5p downregulation or upregulation on hHSFs were subsequently determined. Cell proliferation was detected by an MTT assay, while cell apoptosis was measured by flow cytometry. In addition, the protein expression levels of Smad2, Collagen I (Col I) and Col III were examined by western blot assay. The findings indicated that miR-18a-5p downregulation in hHSFs significantly promoted the cell proliferation, decreased cell apoptosis and enhanced the expression levels of Smad2, Col I and Col III protein and mRNA, whereas miR-18a-5p upregulation in hHSFs exerted opposite effects. Notably, the effects of miR-18a-5p upregulation on hHSFs were eliminated by Smad2 upregulation. In conclusion, the data indicated that miR-18a-5p was downregulated during HS formation, and its upregulation repressed scar fibroblast proliferation and extracellular matrix deposition by targeting Smad2. Therefore, miR-18a-5p may serve as a novel therapeutic target for the treatment of HS.
Insights
MicroRNA-18a-5p (miR-18a-5p) is downregulated in hypertrophic scars (HS). Restoring miR-18a-5p levels inhibits scar fibroblast proliferation and extracellular matrix deposition by targeting Smad2, suggesting its therapeutic potential for HS.
Area of Science:
- Biochemistry
- Molecular Biology
- Dermatology
Background:
- Hypertrophic scarring (HS) is a common fibrotic disorder.
- The molecular mechanisms underlying HS formation require further elucidation.
- MicroRNAs play crucial roles in regulating cellular processes relevant to scarring.
Purpose of the Study:
- To investigate the expression and function of microRNA-18a-5p (miR-18a-5p) in hypertrophic scar (HS) development.
- To explore the molecular targets and pathways regulated by miR-18a-5p in HS fibroblasts.
- To assess the potential of miR-18a-5p as a therapeutic target for HS.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure miR-18a-5p expression.
- Dual-luciferase reporter assay to confirm the binding of miR-18a-5p to Smad2.
- MTT assay for cell proliferation, flow cytometry for apoptosis, and Western blot for protein expression (Smad2, Collagen I, Collagen III).
Main Results:
- miR-18a-5p was significantly downregulated in HS tissues and human HS fibroblasts (hHSFs).
- Downregulation of miR-18a-5p promoted hHSF proliferation, inhibited apoptosis, and increased Smad2, Collagen I, and Collagen III expression.
- Upregulation of miR-18a-5p reversed these effects, and its inhibition by Smad2 upregulation was demonstrated.
Conclusions:
- miR-18a-5p acts as a tumor suppressor in hypertrophic scar formation.
- miR-18a-5p represses scar fibroblast proliferation and extracellular matrix deposition by targeting Smad2.
- miR-18a-5p represents a promising novel therapeutic target for managing hypertrophic scars.
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