Is intrafollicular autophagy an essential mechanism that permits human hair follicles to remain in prolonged anagen in vivo?

Human scalp hair follicles (HF) traverse through a long-lasting cyclical remodelling process during which there is massive growth lasting years. While the genes, transcription and growth factors that regulate HF cycling have long been studied, how human scalp HFs are capable of sustained, energy-intensive proliferation during anagen which lasts for years in vivo. Here, we have probed the hypothesis that autophagy may enable the HF to do this, namely within the anagen hair matrix keratinocytes (MKs). Autophagy is a cellular mechanism that involves degradation and recycling of unnecessary or dysfunctional cellular components by the cell’s lysosomes maintaining cellular energy levels and facilitating cell survival during times of stress or starvation. While autophagy is known to occur other tissues, the role of autophagy in human HF biology remains to be systematically investigated. Therefore we have assessed expression of the key autophagy-related protein LC3B, in human scalp HFs. Utilising immunohistomorphometry, LC3B was found to be mainly expressed in MKs and outer root sheath keratinocytes of anagen HFs, with LC3B protein expression decreasing through catagen ex vivo. This suggests that autophagy is required mainly during anagen. To assess whether autophagy is functionally important for anagen maintenance autophagy was experimentally blocked by silencing the key autophagy gene ATG5 (siRNA) or pharmacologically using chloroquine. Our preliminary results suggest that inhibition of autophagy leads to increased apoptosis in precortical matrix keratinocytes and premature catagen entry. This suggests that intrafollicular autophagy is important for MKs survival during anagen. Taken together, our pilot study provides the first indications that autophagy is important for anagen maintenance in human HF biology. Moreover manipulation of this process may be a new target for the future management of human hair growth disorders.