Molecular pathology of wound healing☆
Introduction
The primary function of the skin is to serve as a protective barrier against the environment. Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Skin-wound healing starts immediately after injury and consists of three phases: inflammation, proliferation, and maturation (Fig. 1). These phases proceed with complicated but well-organized interaction between various tissues and cells [1], [2]. Lots of cellular and molecular-biological studies demonstrated that many cytokines, growth factors, and proteases are closely involved in the wound-healing process to complete normal tissue repair after damage [1], [2].
In forensic practice, it is necessary to evaluate the causal relationship between death and any wounds, and forensic pathologists are always required to discriminate antemortem wounds from postmortem damage. Moreover, when the wound is vital, it is necessary to determine how long before death it was sustained. The short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine.
Section snippets
Inflammation
The disruption of the epidermal barrier occurs the release of prestored interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) from keratinocytes. IL-1 and TNF-α alert surrounding cells to barrier damage. In addition, the extravasation of blood constituents follows the disruption of blood vessels by tissue injury causes. The resulting clot induces hemostasis and provides a matrix for the influx of inflammatory cells. Platelets also secrete growth factors such as: epidermal growth factor
Historical background of wound age determination
The short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine. Walcher [11] and Orsos [12] first emphasized, based on their practical experiences, that the determination of wound vitality or wound age was indispensable in forensic practice. In the 1960s, Raekallio developed the biological evidences in wound age determination, with the investigation of the activity of several enzymes at wound sites [13]. Some years later, Berg et
Simultaneous detection of several factors
Recently, Takamiya et al. [43], [44] simultaneously analyzed several cytokines such as IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ, and TNF-α in human dermal wounds for wound age estimation by the use of multiplex beaded array system. IL-10, GM-CSF, IFN-γ, and TNF-α increased from the early phase of dermal wound healing, IL-6 exclusively in the middle phase, IL-2, IL-4, and IL-8 from the middle phase to the late phase [43]. In another combination, IL-5, IL-12p70, IL-13, and IL-17 increased
Bone marrow cells and skin-wound healing
It is well known that hematopoietic stem cells are present in bone marrow for the renewal of circulating hematopoietic cells. Several lines of accumulating evidence demonstrated that bone marrow-derived stem cells/progenitor cells were essentially involved in tissue repair including skin-wound healing [57], [58]. These progenitor cells are recruited to the injured sites from the bone marrow via peripheral circulation under the guidance of chemotactic cytokines. In particular, Bucala et al.
Acknowledgements
We are grateful to Prof. Dr. Wolfgang Eisenmenger (Institute for Legal Medicine, University of Munich, Germany) and Prof. Dr. Peter Betz (Institute for Legal Medicine, University of Erlangen-Nürunberg, Germany) for their critical and instructive supports to our scientific research. We would like to express my sincere thanks to Prof. Dr. Burkhard Madea (Institute for Legal Medicine, University of Bonn, Germany) and Prof. Dr. Pekka Saukko (Department of Forensic Medicine, University of Turku) for
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This paper is part of the special issue entitled: Molecular Pathology in Forensic Medicine, Guest-edited by Burkhard Madea and Pekka Saukko.