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Gene Therapy in Pathologic Scars

  • Chenyu Huang
  • Longwei Liu
  • Zhifeng You
  • Yanan Du
  • Rei Ogawa
Chapter

Abstract

Hypertrophic scars (HSs) and keloids, as the commonly seen pathological scars, are characteristic of rampant proliferation of fibroblasts, accumulation of collagens in the ECM, and altered regulation of growth factors/cytokines. Though their etiology still remains unclear and the postsurgical recurrence keeps a high profile, great efforts have been made on potential gene therapies for more specific, long-lived and hopefully cheaper results, thanks to the update progress in gene therapy techniques. Here we classify the current gene therapy strategies for HSs and keloids on their targets of cellular behavior, extracellular collagen production, or growth factors/chemokines involved. Namely, (1) gene therapies that alter the balance between cellular proliferation and apoptosis by inducing fibroblast apoptosis or decreasing its proliferation, using suicide gene tools or manipulating miRNA-21 levels respectively; (2) gene therapies that alter the balance between collagen synthesis and degradation focusing on directly reducing collagen production through miRNA-29b or inducing collagen degradation through TIMP siRNAs, or decreasing collagen accumulation through PAI-1-targeting siRNAs or HSP47-siRNAs. In particular, the interfibrillar bonding of collagens is also successfully regulated by antisense oligonucleotides of the non-collagen matrix ingredients (e.g. decorin) and thereby interfering in collagen remodeling; and (3) gene therapies that alter the balance between pro-fibrotic and anti-fibrotic growth factors/cytokines. Different TGF-β subtypes, their receptors, and the TGF-β signaling pathway molecules demonstrate to be potential gene therapy candidates in scar treatments. A better understanding of the current progress in gene therapies for pathological scars will lead to the development of novel interventions that can prevent, reduce, or even reverse the formation and/or progression of HSs or keloids.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Chenyu Huang
    • 1
  • Longwei Liu
    • 2
  • Zhifeng You
    • 2
  • Yanan Du
    • 2
  • Rei Ogawa
    • 3
  1. 1.Department of DermatologyBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua UniversityBeijingChina
  2. 2.Department of Biomedical Engineering, School of MedicineTsinghua UniversityBeijingChina
  3. 3.Department of Plastic, Reconstructive and Aesthetic SurgeryNippon Medical SchoolTokyoJapan

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