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

IF 6 Q2 GERIATRICS & GERONTOLOGY

npj aging Pub Date : 2025-09-26 DOI:10.1038/s41514-025-00268-3

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

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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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解码皮肤老化：KNG1在胶原蛋白和弹性纤维降解中的作用。

Kininogen-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确切作用尚未充分阐明。定量4D蛋白质组测序分析发现，3月龄和15月龄C57BL/6J小鼠皮肤中KNG1表达上调，免疫组织化学染色证实其内在衰老增加。小鼠皮肤中KNG1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Lamin B1，并增加了氧化应激标志物8-羟基-2'-脱氧鸟苷（8-OHdG），而KNG1的下调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潜在的机制。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，通过环氧化物水解酶2 （EPHX2）升高氧化应激。因此，KNG1可能作为一种内在的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，通过EPHX2促进氧化应激。KNG1下调可能是一个潜在的抗衰老靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

npj aging

CiteScore

8.90

自引率

0.00%

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