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

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.