Premium
The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid‐related bioactivity over retinol and retinyl palmitate in human skin models
Author(s) -
Bjerke Donald L.,
Li Rui,
Price Jason M.,
Dobson Roy L. M.,
Rodrigues MyriamRubecca,
Tey ChingSiang,
Vires Laura,
Adams Rachel L.,
Sherrill Joseph D.,
Styczynski Peter B.,
Goncalves Kirsty,
Maltman Victoria,
Przyborski Stefan,
Oblong John E.
Publication year - 2021
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14219
Subject(s) - retinoid , retinyl palmitate , retinol , keratinocyte , human skin , endocrinology , chemistry , retinoic acid , dermis , in vivo , medicine , ex vivo , fenretinide , vitamin , biology , biochemistry , in vitro , anatomy , genetics , microbiology and biotechnology , gene
Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids using in vitro and ex vivo skin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67 and filaggrin. A retinoic acid receptor‐alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results from ex vivo skin found that RP and ROL have higher penetration levels compared with RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14‐hydroxy‐4,14‐ retro ‐retinol (14‐HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm.