Cell and Tissue Research

, Volume 351, Issue 1, pp 117–125

Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair

  • Robert C. Caskey
  • Myron Allukian
  • Robert C. Lind
  • Benjamin J. Herdrich
  • Junwang Xu
  • Antoneta Radu
  • Marc E. Mitchell
  • Kenneth W. Liechty
Regular Article

DOI: 10.1007/s00441-012-1504-7

Cite this article as:
Caskey, R.C., Allukian, M., Lind, R.C. et al. Cell Tissue Res (2013) 351: 117. doi:10.1007/s00441-012-1504-7

Abstract

Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decrease inflammation and promote regenerative healing. To test this hypothesis, the flanks of adult C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound phenotype was assessed by histology to examine tissue architecture and immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds demonstrated the restoration of the normal dermal elements and organized collagen fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal architecture and demonstrated a disorganized collagen scar. At 3 and 7 days, wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1 over-expression promotes dermal regeneration, in part by decreasing the inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA content.

Keywords

Regenerative healing Scar Inflammation Hyaluronan Mouse (C57Bl/6) 

Abbreviations

ECM

Extracellular matrix

HMW-HA

High-molecular-weight hyaluronon

HA

Hyaluronon (hyaluronic acid)

HAS

Hyaluronic acid synthase

LMW-HA

Low-molecular-weight hyaluronon

ROS

Reactive oxygen species

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Robert C. Caskey
    • 1
  • Myron Allukian
    • 2
  • Robert C. Lind
    • 3
  • Benjamin J. Herdrich
    • 2
  • Junwang Xu
    • 5
  • Antoneta Radu
    • 4
  • Marc E. Mitchell
    • 1
  • Kenneth W. Liechty
    • 5
  1. 1.Department of SurgeryUniversity of Mississippi Medical CenterJacksonUSA
  2. 2.Department of SurgeryUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of SurgeryThe University Medical Center GroningenGroningenNetherlands
  4. 4.The Center for Fetal ResearchThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  5. 5.Department of SurgeryNemours Children’s HospitalOrlandoUSA

Personalised recommendations