Notch signaling in bone marrow mesenchymal stem cells induced by li-popolysaccharide / 中国病理生理杂志

ABSTRACT

AIM:To investigate the roles of Notch signaling in lipopolysaccharide(LPS)-induced proliferation and secretion of interleukin-6(IL-6)and chemokine CXCL1 in bone marrow mesenchymal stem cells(BMSCs). METHODS:BMSCs were isolated by whole bone marrow culture.The expression levels of Notch signaling pathway recep-tors and ligands in the BMSCs treated with LPS were measured by qPCR and Western blot.The proliferation of BMSCs was analyzed by MTT assay and viable cell counting.The secretion levels of IL-6 and CXCL1 induced by LPS were measured by ELISA.RESULTS:Treatment with LPS at 1 mg/L effectively induced the proliferation of BMSCs and the secretion of IL-6.Obvious expression of Notch receptors and ligands in the BMSCs was observed,and LPS had little effect on the mRNA and protein levels of Notch receptors and ligands,but LPS increased the protein levels of Hes1 and Hey1,the target genes of Notch signaling.LPS at 1 mg/L increased the proliferation of BMSCs,whereas DAPT(Notch signal inhibitor)reduced the basal and LPS-induced proliferation of BMSCs(P<0.01).LPS treatment robustly increased the secretion of IL-6 and CXCL1 as assessed by ELISA.However,inhibition of Notch signaling almost completely abolished LPS-induced secretion of IL-6 and CXCL1(P <0.05).CONCLUSION: Inhibition of Notch signaling reduced not only the proliferation of BMSCs but also IL-6 and CXCL1 secretion induced by LPS.