Date Published: June 10, 2019
Publisher: Public Library of Science
Author(s): Jolanta Idkowiak-Baldys, Uma Santhanam, Sean M. Buchanan, Kathleen Lindahl Pfaff, Lee L. Rubin, John Lyga, Carol Feghali-Bostwick.
Growth differentiation factor 11 (GDF11) belongs to the TGF-β superfamily of proteins and is closely related to myostatin. Recent findings show that GDF11 has rejuvenating properties with pronounced effects on the cardiovascular system, brain, skeletal muscle, and skeleton in mice. Several human studies were also conducted, some implicating decreasing levels of circulating GDF11 with age. To date, however, there have not been any reports on its role in human skin. This study examined the impact of GDF11 on human skin, specifically related to skin aging. The effect of recombinant GDF11 on the function of various skin cells was examined in human epidermal keratinocytes, dermal fibroblasts, melanocytes, dermal microvascular endothelial cells and 3D skin equivalents, as well as in ex vivo human skin explants. GDF11 had significant effects on the production of dermal matrix components in multiple skin models in vitro and ex vivo. In addition, it had a pronounced effect on expression of multiple skin related genes in full thickness 3D skin equivalents. This work, for the first time, demonstrates an important role for GDF11 in skin biology and a potential impact on skin health and aging.
Aging is defined as the progressive accumulation of diverse deleterious changes in cells and tissues with advancing age that increase the risk of disease and death. Not surprisingly, there is considerable interest in delaying this progression, and research aimed at understanding the aging process and identifying treatments that might slow or even reverse age-related changes is a burgeoning field.
This paper presents data that support a role for circulating GDF11 as a regulator of skin biology. When different skin models including monolayer, 3D tissue skin equivalents, and surgically removed skin explants were treated with physiologically-relevant levels of rGDF11, significant effects on the production of procollagen I and hyaluronic acid were observed. In addition, a decrease in the production of melanin was also observed in melanocytes and 3D skin equivalents. Treatment of full thickness 3D skin equivalents with rGDF11 led to changes in expression of multiple genes that are linked to several important skin functions. Finally, we showed that GDF11 appears to be acting in skin via the Smad2/3 signaling pathway, consistent with it being a member of the TGF-β family.