Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators

Tarek El-Hamoly, Csaba Hegedűs, Petra Lakatos, Katalin Kovács, P. Bai, Mona A. El-Ghazaly, Ezzeddin S. El-Denshary, Éva Szabó, L. Virag

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Poly(ADP-ribosyl)ation (PARylation) is a protein modification reaction regulating various diverse cellular functions ranging from metabolism, DNA repair and transcription to cell death. We set out to investigate the role of PARylation in wound healing, a highly complex process involving various cellular and humoral factors. We found that topically applied poly[ADP-ribose] polymerase (PARP) inhibitors 3-aminobenzamide and PJ-34 accelerated wound closure in a mouse model of excision wounding. Moreover, wounds also closed faster in PARP-1 knockout mice as compared with wild-type littermates. Immunofluorescent staining for poly(ADP-ribose) (PAR) indicated increased PAR synthesis in scattered cells of the wound bed. Expression of interleukin (IL)-6, tumor necrosis factor (TNF)-á, inducible nitric oxide synthase and matrix metalloproteinase-9 was lower in the wounds of PARP-1 knockout mice as compared with control, and expression of IL-1â, cyclooxygenase-2, TIMP-1 and -2 also were affected. The level of nitrotyrosine (a marker of nitrating stress) was lower in the wounds of PARP-1 knockout animals as compared with controls. In vitro scratch assays revealed significantly faster migration of keratinocytes treated with 3-aminobenzamide or PJ34 as compared with control cells. These data suggest that PARylation by PARP-1 slows down the wound healing process by increasing the production of inflammatory mediators and nitrating stress and by slowing the migration of keratinocytes.

Original languageEnglish
Pages (from-to)363-371
Number of pages9
JournalMolecular Medicine
Volume20
Issue numberJULY-DECEMBER 2014
DOIs
Publication statusPublished - 2014

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Keratinocytes
Wound Healing
Adenosine Diphosphate
Wounds and Injuries
Knockout Mice
Poly Adenosine Diphosphate Ribose
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 9
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Interleukin-1
DNA Repair
Interleukin-6
Cell Death
Tumor Necrosis Factor-alpha
Poly (ADP-Ribose) Polymerase-1
Staining and Labeling
Proteins
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. / El-Hamoly, Tarek; Hegedűs, Csaba; Lakatos, Petra; Kovács, Katalin; Bai, P.; El-Ghazaly, Mona A.; El-Denshary, Ezzeddin S.; Szabó, Éva; Virag, L.

In: Molecular Medicine, Vol. 20, No. JULY-DECEMBER 2014, 2014, p. 363-371.

Research output: Contribution to journalArticle

El-Hamoly, T, Hegedűs, C, Lakatos, P, Kovács, K, Bai, P, El-Ghazaly, MA, El-Denshary, ES, Szabó, É & Virag, L 2014, 'Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators', Molecular Medicine, vol. 20, no. JULY-DECEMBER 2014, pp. 363-371. https://doi.org/10.2119/molmed.2014.00130
El-Hamoly, Tarek ; Hegedűs, Csaba ; Lakatos, Petra ; Kovács, Katalin ; Bai, P. ; El-Ghazaly, Mona A. ; El-Denshary, Ezzeddin S. ; Szabó, Éva ; Virag, L. / Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. In: Molecular Medicine. 2014 ; Vol. 20, No. JULY-DECEMBER 2014. pp. 363-371.
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