Cyclosporine A increases hair follicle growth by suppressing apoptosis‐inducing factor nuclear translocation: a new mechanism

Abstract

Cyclosporine A (CsA) enhances hair growth through caspase-dependent pathways by retarding anagen-to-catagen phase transition in the hair follicle growth cycle. Whether apoptosis-inducing factor (AIF), a protein that induces caspase-independent apoptosis, can regulate the hair follicle cycle in response to CsA is currently unclear. Here, we show that the pro-hair growth properties of CsA are in part due to blockage of AIF nuclear translocation. We first isolate hair follicles from murine dorsal skin. We then used Western blot, immunohistochemistry and immunofluorescence to evaluate the expression and localization of AIF in hair follicles. We also determined whether modulation of AIF was responsible for the effects of CsA at the anagen-to-catagen transition. AIF was expressed in hair follicles during the anagen, catagen and telogen phases. There was significant nuclear translocation of AIF as hair follicles transitioned from anagen to late catagen phase; this was inhibited by CsA, likely due to reduced cyclophilin A expression and attenuated AIF release from mitochondria. However, we note that AIF translocation was not completely eliminated, which likely explains why the transition to catagen phase was severely retarded by CsA, rather than being completely inhibited. We speculate that blockade of the AIF signalling pathway is a critical event required for CsA-dependent promotion of hair growth in mice. The study of AIF-related signalling pathways may provide insight into hair diseases and suggest potential novel therapeutic strategies.

Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

“…ROS inhibits epidermal differentiation through decreasing Notch signaling. Furthermore, inhibiting nuclear translocation of apoptosis-inducing factor (AIF), which was released from mitochondria, retards anagen-to-catagen phase transition of hair follicle growth cycle and leads to decreased hair regeneration ( Lan et al, 2015 ). Further research is needed to reveal if mitochondrial metabolic dysfunction inhibits hair regeneration through regulating HFSCs cell differentiation and its signaling pathway.…”

Status of research on the development and regeneration of hair follicles

“…HF-induced pluripotent stem cells can be induced through gene reprogramming 157 . The HF microenvironment regulates the HF cycle process 163 , 164 . In the future,we will collaborate with other researchers to resolve the problem of hair loss and ensure sustainable clinical applications of effective therapeutic strategies.…”

Intrinsic ROS Drive Hair Follicle Cycle Progression by Modulating DNA Damage and Repair and Subsequently Hair Follicle Apoptosis and Macrophage Polarization

“…Increasing evidence suggests that caspase-dependent apoptosis signalling pathways play an important role in hair cycle transition from the anagen to catagen phase [ 18 , 19 ]. Our recent study showed that cyclosporine A increases hair follicle growth by suppressing AIF nuclear translocation and PARP1 expression, suggesting that the AIF-PARP1-mediated apoptotic pathway, a caspase-independent apoptotic signalling pathway, may be involved in HF transition from anagen to catagen [ 20 ]. However, the roles of AIF-PARP1 and cytochrome c- (Cyto c-) caspase-3 (Cas 3) signalling pathway in hair cycle transition from anagen to catagen and their temporal and spatial regulation are unclear.…”