Preferential crosstalk between perifollicular capillary vessels and dermal papilla cells during hair cycling homeostasis

The tissue-specific capillary system supports the unique function of each organ and dynamically remodels in response to local requirements. In this study, we found that perifollicular vascularization flexibly adjusts to accommodate physiological changes. Notably, not all capillary vessels responded and migrated equally. However, those around the dermal papilla (DP) exhibited preferential mobilization. Treatment with minoxidil, a hair growth agent, significantly increased perifollicular vessel mobilization around the DP, whereas it was inhibited in experimental models of tissue aging, such as those involving vascular endothelial growth factor-neutralizing antibody or testosterone treatment, similar to the physiological tissue aging process. Furthermore, vascular endothelial cells triggered the expression of angiogenic chemokine molecules, including CC chemokine ligand 2 (CCL2), in DP cells, and signaling improved crosstalk between perifollicular vessels and the DP. CCL2 expression changed cyclically in the DP vicinity and significantly decreased in aged skin, and treatment with CCL2-neutralizing antibody decreased perifollicular vascularization and suppressed DP function. These findings indicate that the crosstalk between perifollicular vessels and the DP contributes to hair cycling homeostasis and aging, providing a potential target for the treatment of hair loss and other degenerative skin disorders.