Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells

Title:Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells

Volume: 19 Issue: 8

Author(s): Xiangyu Zhang, Xin Zhang, Lu Chen, Jiaqi Zhao, Ashok Raj, Yanping Wang, Shulin Li, Chi Zhang, Jing Yang*Dong Sun*

Affiliation:

• Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

• Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China

Keywords: Adipose mesenchymal stem cell, exosome, glycolysis, endothelial cells, oxygen, glucose.

Abstract:

Background: Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases.

Objectives: The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis.

Methods: AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression.

Results: Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis via activating the SIX1/HBO1 signaling pathway.

Conclusion: The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.

Cite this article as:

Zhang Xiangyu, Zhang Xin, Chen Lu, Zhao Jiaqi, Raj Ashok, Wang Yanping, Li Shulin, Zhang Chi, Yang Jing*, Sun Dong*, Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells, Current Stem Cell Research & Therapy 2024; 19 (8) . https://dx.doi.org/10.2174/011574888X265623230921045240