The role of defensins in treating skin aging

April 1, 2018|Dermatology News

Most skin-aging treatments work by prodding old fibroblasts and keratinocytes to accelerate the production of important cellular components. For example, retinoids act on retinoic acid receptors to activate collagen genes and deactivate collagenase genes. Glycolic acid, ascorbic acid, and certain growth factors stimulate synthesis of collagen by fibroblasts. Older fibroblasts and keratinocytes are sluggish for many reasons; they do not “hear” signals as well as younger cells do. Glycosaminoglycans such as heparan sulfate can help cells hear these signals. Heparan sulfate, for example, assists in the delivery of growth factors to cells, stabilizes them, and presents them to the receptors on the keratinocytes and fibroblasts, and amplifies cellular response to these factors.

A new angle in antiaging skin care is to create new keratinocytes rather than to stimulate old cells. For the last decade, personal care companies have touted the benefit of putting stem cells in cosmeceuticals, claiming that these cells would rejuvenate skin. However, this proved to be unsubstantiated marketing hype because the stem cells were plant derived (often from apples), had poor shelf life, and could not intercalate between the native skin cells and work with them to have any effect. Stems cells in cosmeceuticals became a point of disdain for savvy scientists.

A new approach to skin rejuvenation is to use agents to stimulate an individual’s own stem cells to form new, young cells. A stem cell known as leucine-rich repeat-containing G-protein–coupled receptor (LGR6+), present in the hair follicle, plays a very important role in the rekeratinization that occurs during wound healing. Recent studies have shown that stimulating the LGR6+ stem cell will result in “fresh” keratinocytes in the epidermis that will improve the skin’s appearance. At this point, we do not know if the LGR6+ stem cell has any effect on fibroblasts. The focus of this column is on the role of the peptide defensin in this process and its potential as a topically applied cosmeceutical ingredient to combat cutaneous aging.

Stem cells

Wounding the skin stimulates LGR6+ stem cells. This occurs when neutrophils in the immune system release defensins in response to injury, and, in turn, defensins activate LGR6+ stem cells. Situated above the follicular bulge, these cells are reported to have the capacity to synthesize all cutaneous cell lineages, including sebaceous gland and interfollicular epidermal cells.^1,2 There are no specific studies that show that the LGR6+ cells generate new fibroblasts, but it seems likely. Transplantation of LGR6+ stem cells into the skin results in increased wound healing, hair follicle genesis, and angiogenesis.³ LGR6+ stem cells repopulate the epidermis by creating new basal stem cells. In regards to skin rejuvenation, it is clear that activated LGR6+ stems cells produce new, younger-acting keratinocytes in the epidermis.