TGFβ signaling regulates lipogenesis in human sebaceous glands cells.
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 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.


RESULTS
We 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.


CONCLUSIONS
TGFβ 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.
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Adrian J
AJ
McNairn
Yanne
Y
Doucet
Julien
J
Demaude
Marion
M
Brusadelli
Christopher B
CB
Gordon
Armando
A
Uribe-Rivera
Paul F
PF
Lambert
Charbel
C
Bouez
Lionel
L
Breton
Géraldine
G
Guasch
D001940:Breast / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005145:Face; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007223:Infant; D050155:Lipogenesis / Q000502:physiology*; D012535:Scalp / Q000166:cytology; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D013909:Thorax / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D005353:Fibronectins; D016212:Transforming Growth Factor beta