Abstract
Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-β) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-β1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds.
Highlights
Skin acts as a barrier, protecting the host from external forces and pathogenic organisms
forkhead boxO-1 (FOXO1) down-regulates oxidative stress by activating antioxidant genes and DNA repair enzymes. This facilitates keratinocyte migration and proliferation and decreases keratinocyte apoptosis, which improves wound healing; (b) FOXO1 stimulates transforming growth factor (TGF)-β promoter activity resulting in the upregulation of TGF-β expression
We have found that FOXO3 did not affect wound healing behavior of keratinocytes in vitro [33], which agrees well with reports that FOXO3 deletion does not affect wound healing in vivo [43]
Summary
Skin acts as a barrier, protecting the host from external forces and pathogenic organisms. Wounds allow foreign materials and organisms entry into the body. The healing process begins immediately after injury and occurs in three phases: inflammation and migration, proliferation, and remodeling and maturation [2]. Inflammation and migration involve degranulation of platelets and recruitment of neutrophils to the site of injury followed by recruitment of other leukocytes such as macrophages, which produce growth factors and cytokines [1,2]. Depending on the size of the wound and specific conditions, proliferation occurs during days 2–7 of wound healing and results in the formation of extracellular matrix and re-epithelialization [3,4]. Remodeling and maturation are the final stages in which the wound stabilizes and the proliferation of cells decrease [1,4]. Apoptosis, programmed cell death, is crucial to the cessation of tissue repair [5,6]
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