Role of oxidative stress in the balding dermal papilla

Abstract

The dermal papillae of the hair follicle control its growth, differentiation and apoptosis via a range of growth factors. These secreted growth factors are known to differ between those of non-balding scalp and those of balding scalp and can even differ in response to a common stimuli – androgen. In balding scalp androgen stimulates the secretion of negative growth factors, while in non-balding scalp androgen is found to exert little or no effect. Dermal papilla cells (DPCs) can be cultured in vitro, however those from balding scalp have been found to undergo premature senescence compared to those from non-balding scalp. A major cause of premature senescence is oxidative stress – the gradual accumulation of reactive oxygen species within the cell causing deleterious loss of function. Reactive oxygen species are known to be mediated in response to androgens and growth factors and in turn may affect growth factor signalling within the cell. Using low oxygen cell culture as a means of reducing oxidative stress, balding and non-balding DPCs were grown and characterised. It was confirmed that low oxygen culture could increase proliferation, delay senescence and reduce reactive oxygen species with both DPC types and that balding DPCs showed a higher sensitivity to oxidative stress. It was also found that secretions of growth factors by the balding DPCs in response to different oxygen conditions differed greatly to that of the occipital DPCs. Androgen, but not TGF-β was found to modulate DPC production of catalase, an antioxidant, under low oxygen conditions and this caused a reduction in reactive oxygen species in the balding DPCs. Balding DPCs also demonstrated an upregulation of the antioxidant total glutathione, however had a reduced fraction of the active reduced form of the molecule. In addition, it was shown for the first time 3 that under cell culture conditions balding DPCs express TGF-β receptors and it was shown that proliferation and migration of the balding DPCs could be affected by addition of exogenous TGF-β, highlighting a potential role for TGF-β as an autocrine growth factor in the balding dermal papilla.