PD-L1 vNAR promotes hair growth by modulating hair shaft elongation through activating the leptin-STAT3 signaling.
7 affiliations
- 1Department of Marine Biological Science & Technology, College of Ocean & Earth Sciences, Xiamen University, Xiamen, 361102, China.
- 2Fujian Key Laboratory of Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, College of Geography and Oceanography, Minjiang University, Fuzhou, 350108, China.
- 3The College of Medicine, Xiamen University, Xiamen, 361102, China.
- 4Fujian Key Laboratory of Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, College of Geography and Oceanography, Minjiang University, Fuzhou, 350108, China. [email protected].
- 5Department of Marine Biological Science & Technology, College of Ocean & Earth Sciences, Xiamen University, Xiamen, 361102, China. [email protected].
- 6State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, Xiamen University, Xiamen, 361102, China. [email protected].
- 7Fujian Ocean Innovation Center, Xiamen, 361102, China. [email protected].
Abstract
Programmed death ligand 1 (PD-L1) antibodies have achieved significant success in cancer immunotherapy. However, their roles beyond tumor treatment are not fully understood. In this study, we developed a shark-derived variable new antigen receptor targeting PD-L1, named 3P17, and investigated its role in promoting hair growth in C57BL/6J mice. The intravenous administration of 3P17 increased the proliferation of hair matrix cells, promoted hair shaft elongation, and accelerated hair follicle entry into anagen phage. Moreover, transcriptomic analysis showed that 3P17 increased leptin expression in mouse dorsal skin. Intravenous leptin phenocopied the hair shaft-elongating effect of 3P17. In contrast, the leptin receptor antagonist Allo-aca abrogated 3P17-induced hair shaft elongation. PD-L1, leptin, and phosphorylated STAT3 were co-expressed in hair matrix cells, and both 3P17 and leptin increased STAT3 phosphorylation in mouse dorsal skin. 3P17 also increased the expression of the proliferation-associated genes cyclin D1 and c-Myc in hair follicles. These results collectively indicated that the involvement of leptin-STAT3 signaling in the hair-growth-promoting effect of 3P17. To enhance drug delivery efficiency and patient compliance, we further evaluated the transdermal delivery of leptin using hollow sponge Haliclona sp. spicules (oSHS). oSHS-mediated delivery increased the proportion of leptin penetrating the skin to 43.69 ± 3.66% of the applied dose, representing a 3.28 ± 0.26-fold increase compared with leptin alone. Consistent with this enhanced uptake, oSHS increased leptin deposition into the viable epidermis and dermis, compared with microneedling and SHS, and promoted hair shaft elongation and hair growth in a mouse model of androgenetic alopecia. We propose oSHS-mediated transdermal delivery of leptin as a promising strategy to stimulate hair growth.
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BibTeX
@article{yang2026pdl1,
title = {{PD-L1 vNAR promotes hair growth by modulating hair shaft elongation through activating the leptin-STAT3 signaling.}},
author = {Minghan Yang and Jinlin Chen and Yi Huang and Bowen Zheng and Yunying Cheng and Jianming Chen and Ming Chen},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = aug,
doi = {10.1186/s12964-026-03111-8},
url = {https://europepmc.org/article/MED/42958529},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - PD-L1 vNAR promotes hair growth by modulating hair shaft elongation through activating the leptin-STAT3 signaling.
AU - Minghan Yang
AU - Jinlin Chen
AU - Yi Huang
AU - Bowen Zheng
AU - Yunying Cheng
AU - Jianming Chen
AU - Ming Chen
PY - 2026
DA - 2026/08/03
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03111-8
UR - https://europepmc.org/article/MED/42958529
AB - Programmed death ligand 1 (PD-L1) antibodies have achieved significant success in cancer immunotherapy. However, their roles beyond tumor treatment are not fully understood. In this study, we developed a shark-derived variable new antigen receptor targeting PD-L1, named 3P17, and investigated its role in promoting hair growth in C57BL/6J mice. The intravenous administration of 3P17 increased the proliferation of hair matrix cells, promoted hair shaft elongation, and accelerated hair follicle entry into anagen phage. Moreover, transcriptomic analysis showed that 3P17 increased leptin expression in mouse dorsal skin. Intravenous leptin phenocopied the hair shaft-elongating effect of 3P17. In contrast, the leptin receptor antagonist Allo-aca abrogated 3P17-induced hair shaft elongation. PD-L1, leptin, and phosphorylated STAT3 were co-expressed in hair matrix cells, and both 3P17 and leptin increased STAT3 phosphorylation in mouse dorsal skin. 3P17 also increased the expression of the proliferation-associated genes cyclin D1 and c-Myc in hair follicles. These results collectively indicated that the involvement of leptin-STAT3 signaling in the hair-growth-promoting effect of 3P17. To enhance drug delivery efficiency and patient compliance, we further evaluated the transdermal delivery of leptin using hollow sponge Haliclona sp. spicules (oSHS). oSHS-mediated delivery increased the proportion of leptin penetrating the skin to 43.69 ± 3.66% of the applied dose, representing a 3.28 ± 0.26-fold increase compared with leptin alone. Consistent with this enhanced uptake, oSHS increased leptin deposition into the viable epidermis and dermis, compared with microneedling and SHS, and promoted hair shaft elongation and hair growth in a mouse model of androgenetic alopecia. We propose oSHS-mediated transdermal delivery of leptin as a promising strategy to stimulate hair growth.
SN - 1478-811X
ER -