PLoS Biol. 2018 Mar 28;16(3):e2002864.
Parodi C1, Hardman JA2, Allavena G1, et al.
Autophagy plays a crucial role in health and disease, regulating central cellular processes such as adaptive stress responses, differentiation, tissue development, and homeostasis. However, the role of autophagy in human physiology is poorly understood, highlighting a need for a model human organ system to assess the efficacy and safety of strategies to therapeutically modulate autophagy. As a complete, cyclically remodelled (mini-)organ, the organ culture of human scalp hair follicles (HFs), which, after massive growth (anagen), spontaneously enter into an apoptosis-driven organ involution (catagen) process, may provide such a model. Here, we reveal that in anagen, hair matrix keratinocytes (MKs) of organ-cultured HFs exhibit an active autophagic flux, as documented by evaluation of endogenous lipidated Light Chain 3B (LC3B) and sequestosome 1 (SQSTM1/p62) proteins and the ultrastructural visualization of autophagosomes at all stages of the autophagy process. This autophagic flux is altered during catagen, and genetic inhibition of autophagy promotes catagen development. Conversely, an anti-hair loss product markedly enhances intrafollicular autophagy, leading to anagen prolongation. Collectively, our data reveal a novel role of autophagy in human hair growth. Moreover, we show that organ-cultured scalp HFs are an excellent preclinical research model for exploring the role of autophagy in human tissue physiology and for evaluating the efficacy and tissue toxicity of candidate autophagy-modulatory agents in a living human (mini-)organ.
PMID: 29590104
Taken together, our data support a scenario in which intrafollicular autophagy is eminently targetable for the therapeutic modulation of human hair growth. In line with this concept, another agent that positively regulates autophagy, caffeine [49,50], is sold as a hair growth–promoting cosmeceutical and has been shown to also prolong anagen and stimulate the proliferation of hair MK [51]. Autophagy inducers, which are the focus of intense ongoing research efforts [52–55], are therefore promising agents for the treatment of hair growth disorders and drug-induced hair loss phenomena characterized by premature catagen induction [56]. However, currently available chemical inducers of autophagy have limited specificity for the autophagic process and produce several autophagy-independent effects [55] that may also affect the HF cycle.
