Autophagy is essential for maintaining the growth of a human (mini-)organ: Evidence from scalp hair follicle organ culture

Abstract

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.

Hydroxytyrosol prevents dermal papilla cells inflammation under oxidative stress by inducing autophagy

“…Specifically, our first evidence presents that the protective role of HT is regulated by autophagy in DPCs under OS, as documented by the expression of LC3 protein and presence of LC3B‐fluorescent perinuclear dots (Figure ). As recognized stress‐adaptive mechanism, autophagy prominently manages intrafollicular stress response, and downregulating autophagy does not allow human HFs to support their growth under OS . In addition, FGF is predominantly shown in anagen and preserves HF from cell death caused by the oxidative stressor .…”

Do human dermal adipocytes switch from lipogenesis in anagen to lipophagy and lipolysis during catagen in the human hair cycle?

“…To further test the current hypothesis, immuno‐EM for LC3B and analysing hair cycle‐dependent changes in the number of LC3B+ LDs within the adipocyte cytoplasm/LD are logical next steps. These can be complemented by confocal microscopy of human DAs cocultured with anagen/catagen HFs, and also live‐cell imaging using either deconvolution or super‐resolution microscopy coupled with correlative electron microscopy to detect early formation of ATG9 + autophagic vesicles . Other autophagy‐related techniques are comprehensively covered in including quantification of LC3B/p62 turnover using immunoblotting and detection of autophagolysosomes tagged with GFP labels …”

“…Multiplex platforms may also be employed to check whether DAs engage in secretion of candidate hair growth–modulatory agents during lipophagy inhibition . Additionally, autophagy could be promoted in DAs using commercially available nutritional supplements containing spermidine to investigate how upregulating DA autophagy in human skin can impact upon human HFs …”

Controversy on the role of iron and a clinical trial with intermittent iron and nutritional supplements in hair loss management

“…The process of autophagy is also utilized to disintegrate aggregated, deranged proteins, damaged cell organelles, peroxisomes, endoplasmic reticulum, mitochondria and intracellular pathogens (28). The process of autophagy prevents apoptosis and helps in regenerating worn out cells and cell organelles.…”

“…The process of autophagy prevents apoptosis and helps in regenerating worn out cells and cell organelles. Autophagy has a key role in preventing degenerative disease, autoimmune disorders, infections and cancer (26,27,28). Autophagy is an adaptive mechanism deployed by the hair follicles to survive under conditions of stress.…”