International Journal of Nanomedicine (Sep 2022)

Exosome Derived from Mesenchymal Stem Cells Alleviates Pathological Scars by Inhibiting the Proliferation, Migration and Protein Expression of Fibroblasts via Delivering miR-138-5p to Target SIRT1

  • Zhao W,
  • Zhang R,
  • Zang C,
  • Zhang L,
  • Zhao R,
  • Li Q,
  • Yang Z,
  • Feng Z,
  • Zhang W,
  • Cui R

Journal volume & issue
Vol. Volume 17
pp. 4023 – 4038

Abstract

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Wen Zhao,1 Rui Zhang,1 Chengyu Zang,1 Linfeng Zhang,1 Ran Zhao,1 Qiuchen Li,1 Zhanjie Yang,1 Zhang Feng,1 Wei Zhang,1 Rongtao Cui1,2 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email [email protected]: The therapies of using exosomes derived from mesenchymal stem cells (MSC-Exo) for wound healing and scar attenuation and micro RNAs (miRNAs) for regulation of genes by translational inhibition and mRNA destabilization obtained great achievements. Silent information regulator 1 (SIRT1) is the silent information, which has an intricate role in many biological processes. However, the effects of SIRT1 and miR-138-5p loaded in MSC-Exo on pathological scars remain unclear.Methods: MSC-Exo was isolated and identified by ultracentrifugation, transmission electron microscopy, nanoparticle size measuring instrument and Western blot assays. The relationship between SIRT1 and miR-138-5p was verified by a double-luciferase reporter assay. Cell Counting Kit-8, &Tgr;ranswell, scratch, and Western blot assays were used to evaluate the proliferation and migration of human skin fibroblasts (HSFs), and the protein expression of SIRT1, NF-κB, α-SMA and TGF-β 1 in HSFs, respectively. Flow cytometry was used to assess the apoptosis and cell cycle of HSFs affected by SIRT1.Results: Our study demonstrated that miR-138-5p loaded in MSC-Exo could attenuate proliferation, migration and protein expression of HSFs-derived NF-κB, α-SMA, and TGF-β 1 by targeting to SIRT1 gene, which confirmed the potential effects of MSC-Exo in alleviating pathological scars by performing as a miRNA’s delivery vehicle.Conclusion: Exosomes derived from MSCs acting as a delivery vehicle to deliver miR-138-5p can downregulate SIRT1 to inhibit the growth and protein expression of HSFs and attenuate pathological scars.Keywords: mesenchymal stem cell-derived exosomes, miR-138-5p, SIRT1, human skin fibroblasts, pathological scars

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