Abstract
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.
Data availability
Sequence data that support the findings of this study have been deposited in the NCBI with the primary accession code GSE282648.
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Acknowledgements
The authors thank Ryohei Arai, Akiko Takaoka, and Toru Nagahama for their helpful discussions. We also thank Yoshimi Abe, Ayaka Iwasaki, and Sakiho Koyama for excellent technical assistance.
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Conceptualization: K.M.; Methodology: Y.Z., M.M., H.M., M.I., and K.M.; Investigation: Y.Z., S.T., M.K., R.K., M.K-S., and K.M.; Writing—Original Draft: K.M.; Writing—Review & Editing: all the authors.; Supervision: T.O., M.T., M.I., M.E., and K.M.
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The author Akinari Abe is regular employee of Taisho Pharmaceutical Co., Ltd. However, the funder did not have any additional role in the study design, data analysis, decision to publish, or manuscript preparation. This does not alter our adherence to Nature Portfolio policies on sharing data and materials. All other authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Zeng, Y., Abe, A., Takashima, S. et al. Preferential crosstalk between perifollicular capillary vessels and dermal papilla cells during hair cycling homeostasis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46001-2
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DOI: https://doi.org/10.1038/s41598-026-46001-2
