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MTORC1 activity negatively regulates human hair follicle growth and pigmentation

ABSTRACT: Dysregulation of the activity of mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to ageing, cancer and genetic disorders such as tuberous sclerosis (TS), a rare neurodevelopmental multi-systemic disease characterized by benign tumors, seizures and intellectual disability. Although patches of white hair on the scalp (poliosis) are considered as early signs of TS, the underlying molecular mechanisms and potential involvement of mTORC1 in hair depigmentation remain unclear. Here, we use healthy, organ-cultured human scalp hair follicles (HFs) to interrogate the role of mTORC1. Grey/white HFs exhibit high mTORC1 activity, while mTORC1 inhibition by rapamycin stimulated HF growth and pigmentation. Mechanistically, this occurred via increased intrafollicular production of the melanotropic hormone -MSH, even in grey/white HFs that still contained some surviving melanocytes. In contrast, knockdown of intrafollicular TSC2, a negative regulator of mTORC1, significantly reduced HF pigmentation. Our findings introduce mTORC1 activity as an important negative regulator of human HF growth and pigmentation, and suggest that pharmacological mTORC1 inhibition could become a novel strategy in the management of hair loss and depigmentation disorders.

SUBMITTER: Takahiro Suzuki

PROVIDER: S-SCDT-10_15252-EMBR_202256574 | biostudies-other |

REPOSITORIES: biostudies-other

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