Abstract
All-trans retinoic acid (RA) is an effective anti-aging chemical substance widely used in skin-care products. RA compromises epidermal differentiation and induces keratinocyte proliferation, causing hyaluronic acid production through mechanisms that are not completely understood. Klotho protein causes the differentiation of human epidermal keratinocytes. Klotho gene expression is mediated by epidermal growth factor (EGF), which inhibits cell apoptosis in aging-related diseases. The klotho gene causes human aging syndrome, including short lifespan, skin atrophy, and osteoporosis. We investigated the relationship between RA and klotho in epidermal keratinocytes for the first time. In human epidermal keratinocytes, RA induced klotho gene expression. Treatment with both RA and recombinant klotho induced hyaluronic acid production in human epidermal keratinocytes. However, in klotho small interfering RNA (siRNA)-transfected keratinocytes, RA produced less hyaluronic acid than in the control group, indicating that RA may partially regulate hyaluronic acid production through a klotho-dependent pathway. Knockdown of klotho gene expression inactivated the EGFR-extracellular signal-regulated kinase (ERK) signaling pathway, which is involved in hyaluronic acid production. We concluded that the effect of RA on hyaluronic acid production is partly regulated through the klotho-mediated EGFR signaling pathway in human epidermal keratinocytes.
Highlights
Vitamin A and its retinoid derivatives are important regulators of keratinocyte proliferation and differentiation
We found that retinoic acid (RA) increased klotho gene expression in keratinocytes and increased hyaluronic acid production
Because epidermal growth factor receptor (EGFR) signaling in epidermal keratinocytes mediates RA-induced hyaluronan production [4], we checked if klotho mediates the EGFR-extracellular signal-regulated kinase (ERK) signaling pathway
Summary
Vitamin A and its retinoid derivatives are important regulators of keratinocyte proliferation and differentiation. RA stimulates keratinocyte proliferation, leading to thickening of the epidermis [1]. RA stimulates hyaluronan production in human skin organ cultures and human keratinocyte cultures [2-3]. RA-induced hyaluronan production is partly mediated by epidermal growth factor receptor (EGFR) signaling in epidermal keratinocytes [4]. EGF upregulates the hyaluronan synthases Has and Has involved in epidermal proliferation and differentiation in organotypic keratinocyte cultures [5]. The molecular mechanism between retinoic acid and the EGFR signaling pathway is not completely known
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
