TGFß signaling regulates lipogenesis in human sebaceous glands cells.

ABSTRACT

BACKGROUND: Sebaceous glands are components of the skin essential for its normal lubrication by the production of sebum. This contributes to skin health and more importantly is crucial for the skin barrier function. A mechanistic understanding of sebaceous gland cells growth and differentiation has lagged behind that for keratinocytes, partly because of a lack of an in vitro model that can be used for experimental manipulation. METHODS: We have developed an in vitro culture model to isolate and grow primary human sebocytes without transformation that display functional characteristics of sebocytes. We used this novel method to probe the effect of Transforming Growth Factor ß (TGFß) signaling on sebocyte differentiation, by examining the expression of genes involved in lipogenesis upon treatment with TGFß1. We also repressed TGFß signaling through knockdown of the TGFß Receptor II to address if the effect of TGFß activation is mediated via canonical Smad signal transduction. RESULTS: We find that activation of the TGFß signaling pathway is necessary and sufficient for maintaining sebocytes in an undifferentiated state. The presence of TGFß ligand triggered decreased expression in genes required for the production of characteristics sebaceous lipids and for sebocyte differentiation such as FADS2 and PPARγ, thereby decreasing lipid accumulation through the TGFß RII-Smad2 dependent pathway. CONCLUSION: TGFß signaling plays an essential role in sebaceous gland regulation by maintaining sebocytes in an undifferentiated state. This data was generated using a novel method for human sebocyte culture, which is likely to prove generally useful in investigations of sebaceous gland growth and differentiation. These findings open a new paradigm in human skin biology with important implications for skin therapies.