The transplantation of mesenchymal stem cells (MSCs) is considered to be a promising treatment for ischemic heart disease; however, the therapeutic effects and underlying mechanisms of action require further evaluation. Mitochondrial dysfunction is a key event in simulated ischemia/reperfusion (SI/R) injury. The purpose of the present study was to investigate the mechanism of mitochondrial transfer, which may be involved the antiapoptotic action of co-culture with MSCs. An in vitro model of simulated ischemia/reperfusion (SI/R) was used in the present study. The apoptotic indexes were significantly increased when H9c2 cardiomyocytes were induced in the SI/R group. Following co-culture with bone marrow-derived (BM)-MSCs, H9c2 cells exhibited marked resistance against the SI/R-induced apoptotic process. Besides, mitochondrial transfer via a tunneling nanotube (TNT) like structure was detected by confocal fluorescent microscopy. In addition, following pretreated with latrunculin-A (LatA), an inhibitor of TNT formation, the BM-MSCs were not able to rescue injured H9c2 cells from apoptosis, as previously observed. In conclusion, the anti-apoptotic ability of BM-MSCs may be partially attributed to the recovery of mitochondrial dysfunction in SI/R, and the formation of TNTs appears to be involved in this action of mitochondrial transfer between adjacent cells.

BackgroundCardiovascular disease is the leading cause of death in patients with chronic kidney disease. A body of evidence suggests that p-cresyl sulfate (PCS), a uremic toxin, is associated with the cardiovascular mortality rate of patients with chronic kidney disease; however, the molecular mechanisms underlying this feature have not yet been fully elucidated.Methods and ResultsWe aimed to determine whether PCS accumulation could adversely affect cardiac dysfunction via direct cytotoxicity to cardiomyocytes. In mice that underwent 5/6 nephrectomy, PCS promoted cardiac apoptosis and affected the ratio of left ventricular transmitral early peak flow velocity to left ventricular transmitral late peak flow velocity (the E/A ratio) observed by echocardiography (n=8 in each group). Apocynin, an inhibitor of NADPH oxidase activity, attenuates this alteration of the E/A ratio (n=6 in each group). PCS also exhibited proapoptotic properties in H9c2 cells by upregulating the expression of p22phox and p47phox, NADPH oxidase subunits, and the production of reactive oxygen species. Apocynin and N-acetylcysteine were both able to suppress the effect of PCS, underscoring the importance of NADPH oxidase activation for the mechanism of action.ConclusionsThis study demonstrated that the cardiac toxicity of PCS is at least partially attributed to induced NADPH oxidase activity and reactive oxygen species production facilitating cardiac apoptosis and resulting in diastolic dysfunction.

The insulin‐like growth factor receptor I (IGF‐IR) is a proto‐oncogene with potent mitogenic and antiapoptotic activities. It has been reported that expression of IGF‐IR is up‐regulated in bladder cancer. Here, we assessed whether microRNA‐145 (miR‐145) regulates IGF‐IR expression in bladder cancer. In our study, miR‐145 was shown to directly target IGF‐IR 3′‐untranslated region (UTR) in human bladder cancer cells. Small interfering RNA (siRNA)‐ and miR‐145‐mediated IGF‐IR knockdown experiments revealed that miR‐145 promotes cell apoptosis, and suppresses cell proliferation and migration through suppression of IGF‐IR expression. Taken together, our data suggest that miR‐145 may inhibit bladder cancer initiation by affecting IGF‐IR signaling.