Mesenchymal stem cell conditioned medium alleviates oxidative stress injury induced by hydrogen peroxide via regulating miR143 and its target protein in hepatocytes

Abstract

BackgroundTo investigate the impact of miRNA (microRNA) on hepatic oxidative stress damage under the human mesenchymal stem cell conditioned medium (MSC-CM) and explore the roles of the beta-1 adrenergic receptor (ADRB1) and hexokinase 2 (HK2) in this process.MethodsHydrogen peroxide was used to induce oxidative stress injury in the human normal liver cell line L02. MSC-CM was separately prepared. After treatment with MSC-CM, the protective effects of MSC-CM on oxidative stress injury were assessed by changes in apoptosis, cell viability, cell cycle, and mitochondrial membrane potential. According to the microarray analysis, 19 disparately expressed miRNAs were selected for RT-PCR and miR143 identified as having significant differential expression in MSC-CM against oxidative stress injury. Subsequently, the predicted target proteins of miR143 were selected by bioinformatics software, and verified by western blot. In addition, down-regulation and up-regulation of miR143 expression and hydrogen peroxide induced hypoxia injury were carried out on L02 cells to study the role of miR143.ResultsMSC-CM significantly attenuated H2O2 induced oxidative stress injury. The expression of miR143 was increased following oxidative stress injury whereas it decreased after MSC-CM treatment. The expression levels of HK2 and ADRB1 regulated by miR143 and Bcl-2 decreased under H2O2 treatment but were restored following MSC-CM treatment. However the expression levels of Bax and BMF increased after H2O2 injury and decreased after MSC-CM treatment. Moreover over-expression or down-regulation of miR143 aggravated or alleviated hepatocyte apoptosis respectively.ConclusionsMSC-CM may alleviate H2O2 induced oxidative stress injury by inhibiting apoptosis and adjusting miRNA expression. Moreover down-regulation of miR143 protects L02 cells from apoptosis and initiates an adaptive process by adjusting the expression of HK2 ADRB1 and apoptosis-related proteins.Electronic supplementary materialThe online version of this article (10.1186/s12865-017-0232-x) contains supplementary material, which is available to authorized users.

Effect of Methyl Mercury on the Cerebellar Cortex of Rats and the Possible Neuroprotective Role of Mesenchymal Stem Cells Conditioned Medium. Histological and Immunohistochemical Study

“…CM is a promising novel approach for repairing of wound and tissue regeneration and is also a remedy for neurological diseases as cerebral injury, ischemia and stroke through reducing neuronal cells injuries and enhancing the neuronal glial viability [37,38].…”

“…The previous results agreed with those of other researchers [16,39], who in their studies on the CM showed remyelination of the CNS and reduced astrogliosis, which were supported by significant decrease of GFAP positive immunostaining. It is accepted by many colleagues [16,38,40] that MSCs -CM could improve angiogenesis by its effect on VEGF and resolve inflammation through promoting secretion of antiinflammatory substances, which inhibit fibrosis, apoptosis and necrosis after acute organ injury. Furthermore, it contains various growth factors i.e., Vascular Endothelial Growth Factor (VEGF), Platelet Derived Growth Factor (PDGF), Insulin Like Growth Factor-1 (IGF-1), Neural Growth Factor (NGF), and Brain Derived Neurotrophic Factor (BDNF).…”

The mesenchymal stem cell secretome as an acellular regenerative therapy for liver disease

“…A dose-dependent increase in expression of the anti-apoptotic Bcl2, and reduction in phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NFkβ) were observed in hucMSC-EV-treated CCl 4 -injured L02 cells. hucMSC-CM attenuated oxidative stress-induced apoptosis by suppressing the expression of miR143 [34]. Notably, when compared with unenhanced BM-MSC secretome product, exosome-enrichment enhanced anti-oxidant activity in both APAP- and H 2 O 2 -induced HepG2 cells in vitro and in vivo following CCl 4 -injury [35].…”

Mixed Diets Reduce the Oxidative Stress of Common Carp (Cyprinus carpio): Based on MicroRNA Sequencing

“…A previous study found that overexpression of miR-143 can aggravate apoptosis and inhibition of proliferation (Borralho et al, 2011). In 2017, Xu et al treated the human normal liver cell line L02 with H 2 O 2 , finding that miR-143 expression increased after oxidative stress injury, and it was further discovered that downregulation of miR-143 protects L02 cells from apoptosis by adjusting the expression levels of HK2 and ADRB1 (Xu et al, 2017). In 2018, Gomes et al found that overexpressed miR-143 can increase oxidative stress by reducing antioxidant enzyme superoxide dismutase 1 (SOD1) expression and increasing reactive oxygen species (ROS) generation (Gomes et al, 2018).…”