Abstract
BackgroundSebaceous 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.MethodsWe 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 β (TGFβ) signaling on sebocyte differentiation, by examining the expression of genes involved in lipogenesis upon treatment with TGFβ1. We also repressed TGFβ signaling through knockdown of the TGFβ Receptor II to address if the effect of TGFβ activation is mediated via canonical Smad signal transduction.ResultsWe find that activation of the TGFβ signaling pathway is necessary and sufficient for maintaining sebocytes in an undifferentiated state. The presence of TGFβ 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 TGFβ RII-Smad2 dependent pathway.ConclusionTGFβ 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.
Highlights
Sebaceous glands are components of the skin essential for its normal lubrication by the production of sebum
To determine the effect of Transforming Growth Factor β (TGFβ) signaling on sebocyte differentiation, we investigated the effect of TGFβ ligands on the primary human sebocytes we established using a novel culture system and skin samples from pediatric donors
Primary sebocytes established from pediatric donors express markers of sebaceous gland differentiation To determine the pathways that regulate primary human sebocytes growth and differentiation, we developed a novel culture method by mimicking the microenvironment of the sebaceous glands in vitro
Summary
Sebaceous glands are components of the skin essential for its normal lubrication by the production of sebum. Sebaceous glands are microscopic glands which secrete an oily substance (sebum) in the hair follicles to lubricate the skin and hair of animals [3]. Their function within the epidermis is to prevent the skin from dehydration and protect the body against infections and physical, chemical and thermal assaults of the environment. The production of sebum is regulated throughout life, and decreases dramatically with age [5] This is associated with increased dryness and fragility of the skin. Several human diseases, such as acne vulgaris, atopic dermatitis, seborrheic dermatitis and primary cicatricial alopecia are thought to be associated with deregulation of the sebaceous glands [4,6,7]
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