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.

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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