Wang HF, Yan PY, Muhammad S, Liu YX, Liu C. Hypoxia-inducible factor-1α/β-catenin axis: A conserved regulatory hub for enhancing stem cell function in tissue regeneration. World J Stem Cells 2026; 18(5): 116050 [DOI: 10.4252/wjsc.v18.i5.116050]
Corresponding Author of This Article
Chun Liu, Chief Physician, Consultant, Dean, Professor, Department of Urology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan 030001, Shanxi Province, China. sxtyliuchun@126.com
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Cell Biology
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Editorial
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Wang HF, Yan PY, Muhammad S, Liu YX, Liu C. Hypoxia-inducible factor-1α/β-catenin axis: A conserved regulatory hub for enhancing stem cell function in tissue regeneration. World J Stem Cells 2026; 18(5): 116050 [DOI: 10.4252/wjsc.v18.i5.116050]
World J Stem Cells. May 26, 2026; 18(5): 116050 Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.116050
Hypoxia-inducible factor-1α/β-catenin axis: A conserved regulatory hub for enhancing stem cell function in tissue regeneration
Hui-Fang Wang, Peng-Yu Yan, Shoaib Muhammad, Yu-Xiang Liu, Chun Liu
Hui-Fang Wang, Shoaib Muhammad, First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Peng-Yu Yan, Chun Liu, Department of Urology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Yu-Xiang Liu, Department of Nephrology, Shanxi Provincial People’s Hospital, Taiyuan 030012, Shanxi Province, China
Author contributions: Liu C designed the overall concept and outline of the manuscript; Wang HF, Yan PY, and Muhammad S contributed to the discussion and design of the manuscript, and manuscript writing; Liu YX translated the manuscript, and made preliminary revisions to the manuscript. Liu YX and Liu C contributed equally to this work and share co-corresponding authorship, they jointly conceived and co-drafted and critically revised the manuscript.
Supported by the Natural Science Research Project of Basic Research Program in Shanxi Province, No. 202203021221268; the National Natural Science Foundation of China, No. 82305030; and the Special Fund from Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, No. CKD/SXMU-2024-04.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Chun Liu, Chief Physician, Consultant, Dean, Professor, Department of Urology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan 030001, Shanxi Province, China. sxtyliuchun@126.com
Received: November 2, 2025 Revised: December 12, 2025 Accepted: January 30, 2026 Published online: May 26, 2026 Processing time: 205 Days and 4.6 Hours
Abstract
This article provides an in-depth commentary on the study by Wang et al, which elucidates that the hypoxia-inducible factor-1α (HIF-1α)/β-catenin axis serves as a core hub regulating the function of peripheral blood mesenchymal stem cells (PBMSCs) under hypoxic conditions. The research confirms that in a hypoxic environment, HIF-1α acts as an upstream regulator by directly binding to and activating the transcription of β-catenin, a relationship that is unidirectional and irreversible. This axis enhances the therapeutic potential of PBMSCs through a dual mechanism: On one hand, it regulates anti-apoptotic proteins while inhibiting pro-apoptotic molecules, significantly improving cell survival and self-renewal capacity; on the other hand, it promotes the secretion of factors such as vascular endothelial growth factor, thereby enhancing angiogenic activity. In a rat myocardial infarction model, PBMSCs overexpressing HIF-1α showed significantly improved retention in the infarcted area, reduced infarct size, and promoted neovascularization - effects that were abolished upon knockdown of β-catenin. This discovery provides a key target for optimizing stem cell therapy for myocardial infarction. By pre-activating this axis in vitro (e.g., via lentiviral vectors or small-molecule regulators), it is possible to standardize and enhance the survival and reparative capacity of PBMSCs in ischemic tissues, holding important translational medical value.
Core Tip: The hypoxia-inducible factor-1α/β-catenin axis functions as a conserved regulatory hub that enhances stem cell survival and angiogenic capacity under hypoxic conditions. This unidirectional signaling pathway, with hypoxia-inducible factor-1α as the upstream driver, coordinates anti-apoptotic and pro-angiogenic responses in stem cells, offering a promising target for improving cell-based therapies in ischemic diseases such as myocardial infarction.
