Phosphoproteomic analysis reveals the mechanisms of human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal aging.

Wenzhuo Yu, Xu Jia, Han Qiao, Di Liu, Yan Sun, Rong Yan, Chenglong Zhang, Na Yu, Yiping Song, Mingying Ling, Zhen Zhang, Xuehui Li, Chuanli Zhao, Yanqiu Xing

Department of Geriatric Medicine, Qilu Hospital of Shandong University, 250012 Jinan, Shandong, China. · pubmed

Paper

Abstract

Aging is a critical biological process, with particularly notable impacts on the kidneys. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of transferring various bioactive molecules, which exhibit beneficial therapeutic effects on kidney diseases. This study demonstrates that exosomes derived from hUC-MSCs ameliorate cellular senescence in the kidneys of naturally aging mice. These exosomes reduce the protein expression of senescence markers and senescence-associated secretory phenotypes (SASP) leading to fewer DNA damage foci and increased expression of the proliferation indicator Ki67. During the aging process, many proteins undergo phosphorylation modifications. We utilized data-independent acquisition (DIA) phosphoproteomics to study kidneys of naturally aging mice and those treated with hUC-MSC-derived exosomes. We observed elevated phosphorylation levels of the differentially phosphorylated proteins, Lamin A/C, at Ser390 and Ser392 sites, which were subsequently verified by western blotting. Overall, this study provides a new molecular characterization of hUC-MSC-derived exosomes in mitigating cellular senescence in the kidneys. SIGNIFICANCE: DIA phosphoproteomics was employed to investigate phosphorylated proteins in the kidney tissues of naturally aging mice with hUCMSC-exos treated. The results demonstrated that the DIA technique detected a higher abundance of phosphorylated proteins. We identified 24 significantly differentially phosphorylated proteins, and found that the phosphorylation of specific Lamin A/C sites is crucial for preventing cellular senescence. This study will help to better reveal the related phosphorylated proteins involved in hUCMSC-exos intervention in the kidneys of naturally aging mice, providing a foundation for future research on specific phosphorylation sites of proteins as potential therapeutic targets for renal aging-related diseases.

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Research summary

The paper investigates the mechanisms by which exosomes derived from human umbilical cord mesenchymal stem cells can mitigate cellular senescence in the kidneys of aging mice. This addresses a fundamental aspect of aging and cellular senescence, which are critical components of the aging process. However, while the findings are solid and contribute to understanding potential therapeutic targets for age-related renal issues, the impact is limited as it primarily focuses on a specific mechanism without broader implications for longevity research.

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