The International Journal of Biochemistry & Cell Biology
The role of apoptosis in wound healing
Section snippets
Cellular changes after wound healing
After injury a great variety of signals are released that not only initiate but regulate all aspects of tissue repair. For decades, histologic analyses revealed that there is a regular sequence of differing cell populations that appeared in an incisional wound (Fig. 1). The role of each different cell population has been investigated and currently a function for most types has been proposed. To determine the function of each population, specific cell types were eliminated to determine whether
Variations in the cellular pattern after injury
Most of the information regarding the phases of tissue repair were determined for incisional wounds. In other types of wounds, especially open wounds, the phases of tissue repair tend to blend together and can co-exist in different locations dependent on the degree of tissue repair. A spectrum of the various phases exists with the inflammatory phase being found in the central open areas while more mature phases are found as one travels towards the original wound edge (Fig. 2). There is
Down-regulation of inflammation and the healing process
A great deal of information is known about what `turns on' the inflammatory and fibroblastic responses, but little is known about what “turns off” inflammation and scar formation. All of the various cellular populations go through phases of rapid proliferation in processes that are tied to known signaling processes. What makes the cells disappear has not been a major focus of investigation. Cell populations must change in order to start the next phase of the healing process. For instance, if
Apoptosis as the method of cellular elimination in wounds
While past studies have suggested some potential signals for the elimination of the various populations of cells in tissue repair, the mechanisms of how the cells disappear needs to be addressed. The cells involved in each phase disappear from a wound by one of three potential mechanisms: necrosis, emigration or apoptosis. Necrosis occurs in pathologic tissue repair but for most wounds, healing proceeds without excessive inflammation and resulting tissue damage. Necrosis clearly induces
Apoptosis signals in specific cell types involved in tissue repair
The first cell to arrive in the wound is the neutrophil. Neutrophils are essential in the defense against invading organisms. Their activity is also blamed for local and distant tissue damage through the release of oxygen free radicals and proteases. A predominant hypothesis for the pathophysiology of acute respiratory distress syndrome, for example, is through the activation of neutrophils in an extensive wound which then enter the systemic circulation and adhere to endothelial cells in the
Role of apoptosis in pathologic tissue repair
Many diseases involve dysregulated apoptosis. Cancer is the obvious process that involves a loss of normal apoptosis leading to uncontrolled cellular proliferation. Excessive apoptosis can also be pathologic in such illnesses as autoimmune diseases. A healing wound must also reach an equilibrium of proliferation and apoptosis to reach a steady state of a totally mature scar. During the inflammatory phase, decreased apoptotic activity may lead to an excessive and uncontrolled inflammatory
Summary
Apoptosis plays an essential role in the orchestration of the rapidly changing populations of cells that are involved in the healing of all tissues. For the vast majority of wounds, the controls of proliferation lead to an expeditious closure of a wound. Occasionally, the balance between increased and decreased cellular numbers loses its balance and leads to pathologic tissue repair. By understanding not only the cellular controls that promote proliferation but also decreasing cell numbers
References (50)
- et al.
Control of scarring in adult wounds by neutralising antibody to transforming growth factor β
Lancet
(1992) - et al.
Short-term treatment in vivo with human interferon alpha-2b results in a selective and persistent normalization of keloidal fibroblast collagen, glycosaminoglycan, and collagenase production in vitro
J. Am. Acad. Dermatol.
(1989) - et al.
Apoptosis down-regulates inflammation under the advancing epithelial wound edge: Delayed patterns in diabetes and improvement with topical growth factors
Surgery
(1997) - et al.
Apoptosis is increased in a model of diabetes-impaired wound healing in genetically diabetic mice
Int. J. Biochem. Cell Biol.
(1997) - et al.
Phagocyte recognition of cells undergoing apoptosis
Immunol. Today
(1993) Apoptosis and cutaneous biology
J. Am. Acad. Dermatol.
(1997)- et al.
Two pathways for induction of apoptosis by ultraviolet radiation in cultured human keratinocytes
J. Invest. Dermatol.
(1997) - et al.
Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels
Cell
(1994) - et al.
The neutrophilic leukocyte in wound repair: A study with antineutrophil serum
J. Clin. Invest.
(1972) - et al.
The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum
Am. J. Pathol.
(1975)
Mononuclear cell modulation of connective tissue function
J. Clin. Invest.
The role of macrophages in wound repair. A review
Plast. Reconstr. Surg.
Antilymphocyte serum and Staphylococcal infection
Nature
Role of T cell-dependent immune system in wound healing
Prog. Clin. Biol. Res.
Studies on inflammation and wound healing: Angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages
Surgery
Growth regulation of skin cells by epidermal cell derived factors: Implications for wound healing
Proc. Natl. Acad. Sci. USA
Physiological actions and clinical applications of transforming growth factor-β (TGF-β)
Growth Factors
Neutralisation of TGFβ-1 and TGFβ-2 or exogenous TGFβ-3 to cutaneous rat wounds reduces scarring
J. Cell. Sci.
Transforming growth factor β-3 (TGFβ-3) accelerates wound healing without alteration of scar prominence
Arch. Surg.
Gamma-interferon inhibits collagen synthesis in vivo in the mouse
J. Clin. Invest.
Regulation of collagen synthesis and messenger RNA levels in normal and hypertrophic scar fibroblasts in vitro by interferon alpha-2b
Wound Rep. Reg.
Effect of γ-interferon on the clinical and biologic evolution of hypertrophic scars and Dupuytren's disease: An open pilot study
Plast. Reconstr. Surg.
Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar
Am. J. Pathol.
Covering by a flap induces apoptosis of granulation tissue myofibroblasts and vascular cells
Wound Rep. Reg.
Hypertrophic scars: Analysis of variables
J. Trauma
Cited by (383)
Deciphering the crosstalk between inflammation and biofilm in chronic wound healing: Phytocompounds loaded bionanomaterials as therapeutics
2024, Saudi Journal of Biological Sciences3D bioprinting bioglass to construct vascularized full-thickness skin substitutes for wound healing
2024, Materials Today BioBioactive materials for in vivo sweat gland regeneration
2024, Bioactive MaterialsLectin: A carbohydrate binding glyoprotein and its potential in wound healing
2023, Bioactive Carbohydrates and Dietary Fibre