The regulation and role of epidermal lipid synthesis.

One of the key functions of the epidermis is to form a barrier between the organism and the outside world. As shown in Fig. 3, disruptions of the barrier result in a cascade of events that ultimately leads to barrier repair. The initial signal that initiates this repair response is unknown. The exocytosis of preformed lipid-enriched lamellar bodies is the first step in this response, which is followed by an increase in lipid synthesis in the epidermis. Our studies demonstrate that this increase in epidermal lipid synthesis is required for the synthesis of new lamellar bodies and repair of the barrier. Inhibition of epidermal lipid synthesis by artificial membranes or drugs impairs barrier recovery by preventing the reformation of lamellar bodies and the continued secretion of lipid. Whether the stimulation of lipid synthesis is primarily regulated by disturbances in barrier function or secondarily by decreases in the lipid content of the cells due to the utilization of lipid for the formation of lamellar bodies is unknown. Additionally, the precise mechanisms by which lipid synthesis is increased (enzyme activation, transcriptional regulation, etc.) remain to be elucidated. The secretion of lipid-containing lamellar bodies results in the reaccumulation of lipid in the intercellular spaces of the stratum corneum and the recovery of normal barrier function. Epidermal lipid synthesis also is probably required to provide lipid for new cell membrane formation to allow for the increase in epidermal cell proliferation, which is stimulated following barrier disruption. Additionally, epidermal lipid synthesis may provide regulatory molecules or crucial substrates that are required for DNA synthesis. Thus, epidermal lipid synthesis plays a key role in the major biological functions of the epidermis, the cutaneous permeability barrier, and cell proliferation.