TGFβ signaling regulates lipogenesis in human sebaceous glands cells

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.

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

“…Keratinocyte hyperproliferation, which may lead to follicular obstruction and comedo formation in acne 19,20 , is inhibited by TGFb 21,22 . Likewise, TGFb decreases sebaceous gland lipid production 23 which is increased and altered in acne 24,25 . Finally, innate immune responses, elicited during microbial colonization by P. acnes 26,27 , may be modulated by TGFb 28 .…”

TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium

“…In the sebaceous (McNairn et al, 2013b) and salivary (Janebodin et al, 2013) glands, inhibition of TGFβ signaling in vitro results in an increase of differentiated, mature structures. Our findings support this trend, by which the loss of TGFβ signaling in the conjunctival epithelium results in an expansion of differentiated goblet cells.…”

Wax Esters: Chemistry and Biosynthesis

“…The great advances in the genomic technology and gene knockout technology allowed identification of some of the genes involved and their function in the biosynthesis of some of the surface lipids. Advances are being made in elucidating the signaling molecules and mechanisms involved in maintaining the function of sebaceous glands (McNairn et al 2013). Progress is also being made in molecular intervention in sebum production to deal with such problems as acne pathology (Sato et al 2013).…”