Skin stratum corneum and keratinocyte DNA synthesis

Skin stratum corneum and keratinocyte DNA synthesis refers to the physiological cycle of epidermal cell renewal and the formation of the skin's primary physical barrier. Keratinocytes in the basal layer undergo DNA synthesis to proliferate, a process essential for maintaining epidermal thickness and replacing cells lost to desquamation (StatPearls: Physiology, Epidermis, 2023). As these cells migrate toward the surface, they undergo a complex differentiation program, eventually losing their nuclei to form the protein-rich, enucleated corneocytes of the stratum corneum (NIH: Keratinocyte Differentiation, 2022). In hyperproliferative disorders such as psoriasis, the rate of keratinocyte DNA synthesis is pathologically accelerated, leading to an immature stratum corneum and impaired barrier function (PubMed: Psoriasis Pathogenesis, 2021). Pharmacological agents target this process either by directly inhibiting DNA replication using antimetabolites like methotrexate or by modulating differentiation through nuclear receptors like the retinoic acid receptor (RAR) (PubChem: Methotrexate, 2024). Because this term describes a complex physiological endpoint involving multiple cellular events and tissue layers rather than a single molecule, it is classified as a biological process rather than a discrete therapeutic target.

Other names

Epidermal proliferationKeratinocyte proliferation and differentiationStratum corneum homeostasisEpidermal DNA synthesis

Inhibition of DNA synthesis via antimetabolite activity (e.g., dihydrofolate reductase inhibition) or modulation of epidermal gene expression through nuclear receptor signaling (e.g., RAR/RXR or VDR activation).