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

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

PMC · DOI: 10.3390/ijms27010086 · International Journal of Molecular Sciences · 2025-12-21

## TL;DR

This paper reviews how PAI-1 influences stem cell differentiation and aging, offering insights into its role in disease and potential therapies.

## Contribution

The paper constructs a PAI-1-centered signaling network linking differentiation and senescence, revealing novel therapeutic perspectives.

## Key findings

- PAI-1 regulates both differentiation and senescence through interconnected signaling pathways.
- The review identifies PAI-1 as a potential therapeutic target for chronic diseases.
- PAI-1's roles in fibrosis, thrombosis, and tumorigenesis are highlighted alongside its core functions.

## 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.

## Linked entities

- **Genes:** SERPINE1 (serpin family E member 1) [NCBI Gene 5054]

## Full-text entities

- **Genes:** SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}
- **Diseases:** fibrosis (MESH:D005355), tumorigenesis (MESH:D063646), thrombosis (MESH:D013927)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12785347/full.md

## References

127 references — full list in the complete paper: https://tomesphere.com/paper/PMC12785347/full.md

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Source: https://tomesphere.com/paper/PMC12785347