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


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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: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.

About the authors

Xiangyu Zhang

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Xin Zhang

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Lu Chen

Department of Nephrology, Affiliated Hospital of Xuzhou Medical University

Email: info@benthamscience.net

Jiaqi Zhao

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Ashok Raj

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Yanping Wang

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Shulin Li

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Chi Zhang

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Email: info@benthamscience.net

Jing Yang

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Author for correspondence.
Email: info@benthamscience.net

Dong Sun

Department of Nephrology, Affiliated Hospital of Xuzhou Medical College

Author for correspondence.
Email: info@benthamscience.net

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