The role of ELOVL4 in regulating keratinocytes differentiation

Skin, the largest organ of our body, plays a vital role in protecting us from external pathogens. It consists of three layers: the epidermis, dermis, and hypodermis. Among these layers, the epidermis is the outermost and thinnest layer, yet it plays a critical role in maintaining skin homeostasis. The epidermis is composed of basal keratinocytes, which are stem cells that undergo maturation and differentiation before being pushed toward the skin's surface. The differentiation ability of keratinocytes is essential for proper skin function. ELOVL4 is an enzyme that synthesizes very long chain fatty acids and is abundantly expressed in the eye, skin, and neural tissue. Recently, it’s reported that Elovl4 deficient mice died from dehydration within few hours after birth and the epidermis development is aberrant and the skin barrier is destructed. However, the molecular mechanisms underlying ELOVL4's regulation of keratinocyte differentiation are not well understood. In our study, we found the expression of ELOVL4 is increased during keratinocytes differentiation as well as the content of lipid droplets (LDs) which contain amounts of fatty acids is increased. Interestingly, further experiments showed that the LDs undergo lipolysis during the differentiation and ELOVL4 regulates this process instead of the formation of LDs by knocking down ELOVL4 with the siRNA. These findings indicate that ELOVL4 plays a crucial role in regulating keratinocyte differentiation by mediating lipolysis. Targeting ELOVL4 could potentially represent a new strategy for optimizing the therapeutic effects on skin diseases such as psoriasis, which is a kind of disease associated with the balance between keratinocytes proliferation and differentiation.