Related Experiment Video

Updated: Jul 1, 2025

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
04:41

Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue

Published on: July 28, 2023

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Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids

Siya Dai1, Mingyuan Xu1, Qianqian Pang2

  • 1Department of Plastic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Shangcheng District, Hangzhou, China.

Burns & Trauma
|March 4, 2024
PubMed
Abstract

Insights

Hypoxic macrophage-derived exosomes (HMDE) promote keloid development by enhancing fibroblast proliferation and migration. Exosomal miR-26b-5p within HMDE drives this process through the PTEN-PI3K/AKT pathway, offering potential therapeutic targets for keloid treatment.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • Keloids are characterized by hypoxia, and macrophage phenotype transitions are implicated in their development.
  • The specific role of microRNAs (miRNAs) in exosomes from hypoxic macrophages concerning keloids is not well understood.
  • This study investigates hypoxic macrophage-derived exosomes (HMDE) and their associated miRNAs in keloid pathogenesis.

Purpose of the Study:

  • To explore the role of HMDE in the occurrence and development of keloids.
  • To identify critical miRNAs within HMDE that influence keloid progression.
  • To elucidate the molecular mechanisms underlying HMDE-mediated effects on keloid fibroblasts.

Main Methods:

  • Immunofluorescence and flow cytometry to analyze macrophage polarization in keloid tissues and under hypoxia.
  • Confocal microscopy to confirm exosome uptake by human keloid fibroblasts (HKFs).
  • miRNA sequencing to identify differentially expressed miRNAs in exosomes; dual-luciferase reporter assay to validate PTEN as a target of miR-26b-5p; functional assays (CCK-8, wound-healing, Transwell) and Western blot to assess biological functions and signaling pathways (PTEN-PI3K/AKT).

Main Results:

  • M2-type macrophages are enriched in keloids, and hypoxia induces macrophage polarization to M2-type.
  • HMDE significantly promote proliferation, migration, and invasion of HKFs compared to normoxic exosomes (NMDE).
  • miR-26b-5p was identified as a key miRNA enriched in HMDE, transferred to HKFs, and found to promote HKF migration, invasion, and proliferation via the PTEN-PI3K/AKT pathway.

Conclusions:

  • Exosomal miR-26b-5p derived from hypoxic macrophages significantly contributes to keloid development.
  • The PTEN-PI3K/AKT signaling pathway is a critical mediator of miR-26b-5p's pro-keloid effects.
  • Targeting exosomal miR-26b-5p presents a potential therapeutic strategy for managing keloids.
Keywords:
ExosomeHypoxiaKeloidMacrophagePhosphatase and tension homologmiR-26b-5p

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