17β-Estradiol promotes angiogenesis of bone marrow mesenchymal stem cells by upregulating the PI3K-Akt signaling pathway

Objective: Estrogen is an important hormone affecting angiogenesis in women and is important for female physical development. Menopausal women are prone to serious cardiovascular and cerebrovascu-lar diseases when estrogen is significantly reduced. Bone marrow mesenchymal stem cells (BMSC) have potential roles in processes such as angiogenesis and remodeling. This study is to investigate the effect of 176-estradiol on BMSC angiogenic differentiation and its underlying molecular mechanism, and to pro-vide a basis for the treatment of microvascular diseases. Methods: Enrichment analysis of apoptosis, migration or angiogenesis processes and molecular mecha-nisms of BMSC treated with 17 beta-estradiol was performed to screen core proteins and perform molecular docking validation. Human MSCs were cultured in vitro to examine the effect of 17 beta-estradiol on BMSC migration or angiogenic differentiation. Results: 17 beta-estradiol acted on 48 targets of BMSC and was involved in regulating 52 cell migration pro-cesses or 17 angiogenesis processes through 66 KEGG pathways such as PI3K-Akt, MAPK, etc. 17 beta-estradiol bound tightly to 10 core proteins including APP, NTRK1, EGFR, and HSP90AA1. 17 beta-estradiol promoted cell scratch area closure rate and CD31 expression in BMSCs, downregulated BMSC apoptosis rate, and promoted Akt and p-Akt protein expression in BMSC. Conclusion: 17 beta-estradiol binds to FN1, MCM2, XPO1, NTRK1 and other proteins to initiate PI3K-Akt, MAPK and other signaling pathways, so as to regulate BMSC to promote or remodel angiogenesis, verifying that 17 beta-estradiol up-regulates PI3K-Akt signaling pathway to promote BMSC angiogenic differentiation. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Automated summary

Estrogen plays an important role in angiogenesis and female physical development. This study investigates the effect of 17β-estradiol on bone marrow mesenchymal stem cell (BMSC) angiogenic differentiation and its underlying molecular mechanism, providing a basis for the treatment of microvascular diseases.