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J Biol Chem. 2014 Sep 26;289(39):27090-104. doi: 10.1074/jbc.M114.580936. Epub 2014 Aug 12.

Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation.

Author information

1
From the Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, 1200 Vienna, Austria, The Austrian Cluster for Tissue Regeneration, Vienna, Austria.
2
From the Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, 1200 Vienna, Austria, The Austrian Cluster for Tissue Regeneration, Vienna, Austria, fuchsc@technikum-wien.at.
3
The Austrian Cluster for Tissue Regeneration, Vienna, Austria, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/Austrian Workers' Compensation Board (AUVA) Research Center, 1200 Vienna, Austria.
4
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/Austrian Workers' Compensation Board (AUVA) Research Center, 1200 Vienna, Austria, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, and.
5
Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.

Abstract

Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing.

KEYWORDS:

ATP; Cell Proliferation; Extracellular Signal-regulated Kinase (ERK); Shock Wave Treatment; Signal Transduction; Wound Healing

PMID:
25118288
PMCID:
PMC4175346
DOI:
10.1074/jbc.M114.580936
[Indexed for MEDLINE]
Free PMC Article

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