Remodeling Lymphatic Vessels in Intrinsically Aged Skin on SKH-1 Mouse Using Low Dose 5-aminolevulinic Acid Photodynamic Therapy via VEGF-C/VEGFR3 Pathway

Yuling Yang; Shuzhan Shen; Yajing Cao; Dixin Wang; Ziwei Kang; Peiru Wang; Xiuli Wang

doi:10.1016/j.pdpdt.2022.102851

Remodeling Lymphatic Vessels in Intrinsically Aged Skin on SKH-1 Mouse Using Low Dose 5-aminolevulinic Acid Photodynamic Therapy via VEGF-C/VEGFR3 Pathway

Photodiagnosis Photodyn Ther. 2022 Jun:38:102851. doi: 10.1016/j.pdpdt.2022.102851. Epub 2022 Apr 6.

Authors

Yuling Yang¹, Shuzhan Shen², Yajing Cao², Dixin Wang², Ziwei Kang², Peiru Wang³, Xiuli Wang⁴

Affiliations

¹ Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, China.
² Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: wangpeiru@tongji.edu.cn.
⁴ Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, China; Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: wangxiuli_1400023@tongji.edu.cn.

PMID: 35398260
DOI: 10.1016/j.pdpdt.2022.102851

Abstract

Background: Decline of lymphatic vessel (LV) density and function in intrinsically aged skin can lead to harmful substance accumulation and fluid imbalance. Whether it will be improved by low dose ALA-PDT needs to be investigated.

Aims: To investigate the effect of low dose ALA-PDT on remodeling LVs in intrinsically aged skin.

Methods: Low dose ALA-PDT with 3 sessions were applied on the dorsal skin of intrinsically aged SKH-1 mice (15 months old). Skin biopsies were obtained from young mice (4 months old, Young-control), intrinsically aged mice before PDT (Old-pre-PDT), and after PDT at different time points (Old-PDT-24h, Old-PDT-1w, Old-PDT-4w), and skin phenotypes were evaluated by dermoscopy. The structure of LVs and extracellular matrix were evaluated via immunofluorescence staining and HE. The drainage function of LVs was evaluated by Evans Blue assay in vivo. The expression of Calcium-binding EGF domain-containing protein 1 (CCBE1), VE-cadherin, and the activation of VEGF-C/VEGFR3 signaling pathway were evaluated by ELISA and Western Blot.

Results: The density of LVs decreased and the lymphatic clearance was significantly delayed in aged skin. Low dose ALA-PDT increased the density of LVs and blood vessels. The clearance of Evans Blue assay showed the drainage function of LVs was improved after PDT treatments in vivo. The VE-cadherin and VEGF-C/VEGFR3 pathway up-regulated in intrinsically aged skin after ALA-PDT treatments.

Conclusions: LVs in intrinsically aged skin were remodeled and their function were restored by low dose ALA-PDT via up-regulating the VEGF-C/VEGFR3 pathway and stimulating the expression of VE-cadherin.

Keywords: Intrinsic aging; Lymphatic vessels; Photodynamic therapy; Skin.

MeSH terms

Aminolevulinic Acid / pharmacology
Animals
Evans Blue
Lymphatic Vessels*
Mice
Photochemotherapy* / methods
Photosensitizing Agents / therapeutic use
Vascular Endothelial Growth Factor C

Substances

Photosensitizing Agents
Vascular Endothelial Growth Factor C
Evans Blue
Aminolevulinic Acid