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Natural compound bavachalcone promotes the differentiation of endothelial progenitor cells and neovascularization through the ROR?-erythropoietin-AMPK axis.

ABSTRACT: In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization in vivo; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis. The BavaC treatment of rat bone marrow cells for 24 h initiated the AMP-activated protein kinase (AMPK) activity required for the differentiation of EPCs. Further testing revealed that BavaC and CGP52608, a retinoic acid receptor-related orphan receptor ? (ROR?) activator, enhanced the activity of ROR?1 and EPO luciferase reporter gene. BavaC treatment also elevated EPO mRNA and protein expression in vitro and in vivo and the circulating EPO levels in rats. By contrast, the ROR? antagonist VPR66 inhibited BavaC-induced EPO reporter activity, and differentiation of bone marrow cells into endothelial progenitor cells. Overall, this study revealed that BavaC promotes EPC differentiation and neovascularization through a ROR?-EPO-AMPK axis. BavaC can be used as a promising angiogenesis agent for enhancing angiogenesis and tissue repair.

SUBMITTER: Ling S

PROVIDER: S-EPMC5689677 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Natural compound bavachalcone promotes the differentiation of endothelial progenitor cells and neovascularization through the RORα-erythropoietin-AMPK axis.

Ling Shuang S Ni Rong-Zhen RZ Yuan Yunyun Y Dang Yan-Qi YQ Zhou Qian-Mei QM Liang Shuang S Guo Fujiang F Feng Wei W Chen Yuanyuan Y Ikeda Katsumi K Yamori Yukio Y Xu Jin-Wen JW

Oncotarget 20170916 49

In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization <i>in vivo</i>; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischem ...[more]

PMID: 29156787

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Project description:The capability to derive endothelial cell (ECs) from induced pluripotent stem cells (iPSCs) holds huge therapeutic potential for cardiovascular disease. This study elucidates the precise role of the RNA-binding protein Quaking isoform 5 (QKI-5) during EC differentiation from both mouse and human iPSCs (hiPSCs) and dissects how RNA-binding proteins can improve differentiation efficiency toward cell therapy for important vascular diseases. iPSCs represent an attractive cellular approach for regenerative medicine today as they can be used to generate patient-specific therapeutic cells toward autologous cell therapy. In this study, using the model of iPSCs differentiation toward ECs, the QKI-5 was found to be an important regulator of STAT3 stabilization and vascular endothelial growth factor receptor 2 (VEGFR2) activation during the EC differentiation process. QKI-5 was induced during EC differentiation, resulting in stabilization of STAT3 expression and modulation of VEGFR2 transcriptional activation as well as VEGF secretion through direct binding to the 3' UTR of STAT3. Importantly, mouse iPS-ECs overexpressing QKI-5 significantly improved angiogenesis and neovascularization and blood flow recovery in experimental hind limb ischemia. Notably, hiPSCs overexpressing QKI-5, induced angiogenesis on Matrigel plug assays in vivo only 7 days after subcutaneous injection in SCID mice. These results highlight a clear functional benefit of QKI-5 in neovascularization, blood flow recovery, and angiogenesis. Thus, they provide support to the growing consensus that elucidation of the molecular mechanisms underlying EC differentiation will ultimately advance stem cell regenerative therapy and eventually make the treatment of cardiovascular disease a reality. The RNA binding protein QKI-5 is induced during EC differentiation from iPSCs. RNA binding protein QKI-5 was induced during EC differentiation in parallel with the EC marker CD144. Immunofluorescence staining showing that QKI-5 is localized in the nucleus and stained in parallel with CD144 in differentiated ECs (scale bar = 50 µm). Stem Cells 2017 Stem Cells 2017;35:952-966.

Dataset Information

Natural compound bavachalcone promotes the differentiation of endothelial progenitor cells and neovascularization through the ROR?-erythropoietin-AMPK axis.

Publications

Natural compound bavachalcone promotes the differentiation of endothelial progenitor cells and neovascularization through the RORα-erythropoietin-AMPK axis.

Similar Datasets

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