Endothelial cells(ECs)not only serve as a barrier between blood and extravascular space to modulate the exchange of fluid,macromolecules and cells,but also play a critical role in regulation of vascular homeostasis and adaptation under mechanical stimulus via intrinsic mechanotransduction.Recently,with the dissection of microdomains responsible for cellular responsiveness to mechanical stimulus,a lot of mechanosensing molecules(mechanosensors)and pathways have been identified in ECs.In addition,there is growing evidence that endothelial mechanosensors not only serve as key vascular gatekeepers,but also contribute to the pathogenesis of various vascular disorders.This review focuses on recent findings in endothelial mechanosensors in subcellular microdomains and their roles in regulation of physiological and pathological functions under mechanical stress.
Embryonic stem cells （ESCs） hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs （lncRNAs） are an important class of gene regulators that play essential roles in a variety of physiologic and pathologic processes. Dozens of lncRNAs are now identified to control ESC self-renewal and differentiation. Research on lncRNAs may provide novel insights into manipulating the cell fate or reprogramming somatic cells into induced pluripotent stem cells （iPSCs）. In this review, we summarize the recent research efforts in identifying functional lncRNAs and understanding how they act in ESCs, and discuss various future directions of this field.
The mitochondria play essential roles in both intracellular calcium and reactive oxygen species signaling.As a newly discovered universal and fundamental mitochondrial phenomenon,superoxide flashes reflect transient bursts of superoxide production in the matrix of single mitochondria.Whether and how the superoxide flash activity is regulated by mitochondrial calcium remain largely unknown.Here we demonstrate that elevating mitochondrial calcium either by the calcium ionophore ionomycin or by increasing the bathing calcium in permeabilized HeLa cells increases superoxide flash incidence,and inhibition of the mitochondrial calcium uniporter activity abolishes the flash response.Quantitatively,the superoxide flash incidence is correlated to the steady-state mitochondrial calcium elevation with 1.7-fold increase per 1.0?F/F0 of Rhod-2 signal.In contrast,large mitochondrial calcium transients(e.g.,peak△F/F0~2.8,duration^2 min)in the absence of steady-state elevations failed to alter the flash activity.These results indicate that physiological levels of sustained,but not transient,mitochondrial calcium elevation acts as a potent regulator of superoxide flashes,but its mechanism of action likely involves a multi-step,slow-onset process.
