Retinoid-responsive transcriptional changes in epidermal keratinocytes

Area of Science:

• Dermatology and Molecular Biology
• Investigating the molecular mechanisms of retinoid action in human skin cells.

Background:

• Retinoids (RA) are established treatments for various skin conditions like acne, psoriasis, and wrinkles.
• The comprehensive molecular effects of RA on epidermal keratinocytes remain incompletely understood.

Purpose of the Study:

• To identify the transcriptional targets of all-trans retinoic acid (RA) in primary human epidermal keratinocytes.
• To elucidate the rapid and broad molecular responses of keratinocytes to RA treatment.

Main Methods:

• Utilized large DNA microarrays to compare transcriptional profiles of keratinocytes exposed to RA over 72 hours.
• Performed in silico analysis to identify over-represented transcription factor binding sites in RA-regulated genes.

Main Results:

• RA rapidly regulates over 300 genes within 1 hour, affecting keratinocyte differentiation and cornification markers.
• Suppression of genes involved in epidermal lipid biosynthesis (fatty acids, cholesterol, sphingolipids) was observed.
• RA activates its own synthesis, esterification, and metabolism pathways, regulating its bioavailability.
• Novel effects on cell cycle, programmed cell death, keratinocyte proliferation, and apoptosis were identified.
• Over one-third of RA-regulated genes are involved in signal transduction and transcriptional regulation.
• RA influences numerous psoriasis-related genes, with both induction and suppression observed.

Conclusions:

• This study provides a comprehensive documentation of RA-induced transcriptional changes in keratinocytes.
• Reveals novel insights into the molecular mechanisms underlying RA's effects on the epidermis.
• Highlights the rapid and extensive impact of RA on keratinocyte biology, including proliferation and apoptosis.