Mobility and regeneration
One of these age-related changes in the human body is a decrease in the ability of the skin to regenerate. However, the molecular and cellular mechanisms underlying this process are currently poorly understood. A group of researchers from the Tokyo Medical and Dental University (TMDU) found that the ability of stem cells to repair skin after injury is associated with their ability to move in the direction of injury.
Skin stem cells (stem keratinocytes) are responsible for skin regeneration and wound closure through the process of reepithelization. In vivo experiments and computer simulations have shown that the mobility of skin stem cells is proportional to their proliferative and regenerative capacity, and old stem cells have significantly reduced mobility.
To understand the mechanisms underlying this decrease in the mobility of old stem cells, the researchers compared the wound healing and proliferative ability of skin stem cells obtained from young (age 12 weeks) and old mice (age 19-25 months). The analysis showed that the epidermal growth factor receptor (EGFR) controls the mobility of skin stem cells and that EGFR signaling in old stem cells is reduced. EGFR prevents the degradation of collagen type 17 (COL17A1), which is necessary for the consolidation of skin layers.
Schematic representation of stem keratinocyte motility mediated by EGFR regulated by COL17A1 signaling. EGFR stabilizes COL17A1 by inducing a tissue metalloproteinase-1 inhibitor (TIMP1), which is necessary for cell mobility coordinated by networks of actin and keratin fibers.
Interestingly, COL17A1 coordinates the movement of skin stem cells to damage by regulating networks of actin and keratin fibers in cells. The researchers found that EGFR signaling decreases with age, which leads to a decrease in COL17A1 levels and the accumulation of skin stem cells with limited mobility, which are less capable of re-epithelization.
A decrease in the healing rate of the skin leads to the development of chronic wounds, including diabetic ulcers and bedsores. Stabilization of COL17A1 by blocking its destruction is a promising approach to increase the ability to regenerate the skin.
Article by D.Nanba et al. EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis published in the Journal of Cell Biology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on TMDU materials: Skin stem cells get moving for enhanced skin regeneration.