解读皮肤衰老：KNG1在胶原蛋白和弹性纤维降解中的作用

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

作者信息

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

机构信息

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.

Guangzhou Dublin International College of Life Sciences and Technology, South China Agricultural University, Guangzhou, China.

出版信息

NPJ Aging. 2025 Sep 26;11(1):80. doi: 10.1038/s41514-025-00268-3.

DOI:10.1038/s41514-025-00268-3

PMID:41006344

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12475185/

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.

摘要

激肽原-1（KNG1）是一种重要的促炎和促氧化因子，但其在皮肤衰老中的精确作用仍未得到充分阐明。定量4D蛋白质组测序分析发现，在3个月和15个月大的C57BL/6J小鼠皮肤中KNG1表达上调，免疫组织化学染色证实其在自然衰老过程中增加。KNG1在小鼠皮肤中的过表达降低了真皮厚度、胶原纤维含量、弹性纤维密度、衰老标志物层粘连蛋白B1，并增加了氧化应激标志物8-羟基-2'-脱氧鸟苷（8-OHdG），而KNG1基因敲低改善了这些与衰老相关的表型。蛋白质-蛋白质相互作用分析揭示了其潜在机制。KNG1通过膜金属内肽酶（MME）活性调节弹性纤维降解，通过基质金属肽酶1（MMP1）和基质金属肽酶9（MMP9）调节胶原纤维降解，并通过环氧水解酶2（EPHX2）提高氧化应激水平。因此，KNG1可能作为一种内源性皮肤衰老生物标志物，通过MMP1/MMP9促进胶原纤维降解，通过MME促进弹性纤维分解，并通过EPHX2促进氧化应激。KNG1的下调可能代表一个潜在的抗衰老靶点。