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RESEARCH PAPER / 2026-01-10

PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.

Jihan Ke, Youping Jiang, Zhiyong Cheng, Yulan Zhou, Jiaxu Lu, Bo Xu, Shouquan Yan, Jiafeng Wang

Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. · pubmed

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is a central regulator of the fibrinolytic system and is increasingly recognized for its pivotal roles in a broad spectrum of physiological and pathological processes. In addition to its classical function in fibrinolysis, accumulating evidence highlights the involvement of PAI-1 in cellular senescence, differentiation, fibrosis, thrombosis, and tumorigenesis. This review systematically summarizes recent advances in understanding the multifaceted biological functions of PAI-1, with a particular emphasis on its dual regulatory roles in cellular differentiation and senescence. Through manual curation and analysis of the literature, we constructed a PAI-1-centered signaling network associated with differentiation and further integrated this framework with known senescence-related pathways. This integrative approach aims to elucidate the crosstalk between differentiation and senescence mediated by PAI-1. By providing an in-depth overview of PAI-1 functions across various experimental models, this review offers a theoretical foundation for exploring its potential as a therapeutic target and presents novel perspectives for the development of intervention strategies for complex chronic diseases.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

PAI-1 plays a dual regulatory role in cellular differentiation and senescence, suggesting its potential as a therapeutic target for chronic diseases related to aging. The paper is relevant as it explores mechanisms that could address the underlying processes of aging rather than merely treating age-related symptoms.

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