Background: Sebaceous glands are components of the skin essential for its normal lubrication by the production\r\nof sebum. This contributes to skin health and more importantly is crucial for the skin barrier function. A mechanistic\r\nunderstanding of sebaceous gland cells growth and differentiation has lagged behind that for keratinocytes, partly\r\nbecause of a lack of an in vitro model that can be used for experimental manipulation.\r\nMethods: We have developed an in vitro culture model to isolate and grow primary human sebocytes without\r\ntransformation that display functional characteristics of sebocytes. We used this novel method to probe the effect\r\nof Transforming Growth Factor �Ÿ (TGF�Ÿ) signaling on sebocyte differentiation, by examining the expression of\r\ngenes involved in lipogenesis upon treatment with TGF�Ÿ1. We also repressed TGF�Ÿ signaling through knockdown\r\nof the TGF�Ÿ Receptor II to address if the effect of TGF�Ÿ activation is mediated via canonical Smad signal\r\ntransduction.\r\nResults: We find that activation of the TGF�Ÿ signaling pathway is necessary and sufficient for maintaining\r\nsebocytes in an undifferentiated state. The presence of TGF�Ÿ ligand triggered decreased expression in genes\r\nrequired for the production of characteristics sebaceous lipids and for sebocyte differentiation such as FADS2 and\r\nPPAR?, thereby decreasing lipid accumulation through the TGF�Ÿ RII-Smad2 dependent pathway.\r\nConclusion: TGF�Ÿ signaling plays an essential role in sebaceous gland regulation by maintaining sebocytes in an\r\nundifferentiated state. This data was generated using a novel method for human sebocyte culture, which is likely to\r\nprove generally useful in investigations of sebaceous gland growth and differentiation. These findings open a new\r\nparadigm in human skin biology with important implications for skin therapies.
Loading....