Decoding skin aging: the role of KNG1 in collagen and elastic fibre degradation.

Xinyue Zhang, Xinyu Yang, Xiaoran Liu, Jianyuan Huang, Yarui Zhang, Xunhong Xu, Qimei Chen, Shan Zhao, Tianyi Huang, Min Zhang, Lin Zhang, Xueer Wang

NMPA Key Laboratory for Safety Evaluation of Cosmetics, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.NMPA Key Laboratory for Safety Evaluation of Cosmetics, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. · pubmed

Paper

Abstract

Kininogen-1 (KNG1) is an important pro-inflammatory and pro-oxidant factor, but its precise role in skin aging remains inadequately elucidated. Quantitative 4D proteomic-sequencing analysis identified upregulated KNG1 in 3- and 15-month-old C57BL/6J mouse skin, with immunohistochemical staining corroborating its increase in intrinsic aging. KNG1 overexpression in murine skin reduced dermal thickness, collagen fibre content, elastic fibre density, aging marker Lamin B1, and increased oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), while KNG1 knockdown ameliorated these aging-associated phenotypes. Protein-protein interaction analysis revealed the underlying mechanisms. KNG1 regulates elastic fibre degradation through membrane metallo-endopeptidase (MME) activity, modulates collagen fibre degradation via matrix metallopeptidase 1 (MMP1) and matrix metallopeptidase 9 (MMP9), and elevates oxidative stress through epoxide hydrolase 2 (EPHX2). Thus, KNG1 may serve as an intrinsic skin aging biomarker, promoting collagen fibre degradation through MMP1/MMP9, elastic fibre breakdown through MME, and oxidative stress through EPHX2. KNG1 downregulation may represent a prospective anti-aging target.

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Research summary

KNG1 regulates collagen and elastic fibre degradation in skin aging and may serve as a potential anti-aging target. The study addresses intrinsic mechanisms of skin aging, focusing on KNG1's role in promoting degradation processes, which aligns with the goal of understanding and potentially mitigating the root causes of aging.

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