Deficiency of Formyl Peptide Receptor 2 Retards Hair Regeneration by Modulating the Activation of Hair Follicle Stem Cells and Dermal Papilla Cells in Mice
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Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient’s psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.
Abstract
Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient’s psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.
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