B7-1 expression regulates the hypoxia-driven cytoskeleton rearrangement in glomerular podocytes

Chang JM, Hwang DY, Chen SC, Kuo MC, Hung CC, Hwang SJ, Tsai JC, Chen HC. B7-1 expression regulates the hypoxia-driven cytoskeleton rearrangement in glomerular podocytes. Am J Physiol Renal Physiol 304: F127-F136, 2013. First published September 26, 2012; doi:10.1152/ajprenal.00108.2012.-Chronic hypoxia has been recognized as a common mechanism driving the progression of many glomerular diseases. Glomerular cells, although susceptible to hypoxic injuries, are less studied to unravel the hypoxia-related influences. In the present study, we showed that both lipopolysaccharide (LPS) and hypoxia induced B7-1 and hypoxia-inducible factor (HIF)-1 alpha expression in podocytes. B7-1, an essential player in the regulation of podocyte stress fibers, interacted directly with the NH2-terminal oxygenation domain of HIF-1 alpha protein and, therefore, might interfere with the HIF-related oxidative events. The suggestion was supported by the changes in the expression of inducible nitric oxide synthase and nitric oxide. The orderly arranged stress fibers in differentiated podocytes were disrupted by either LPS or hypoxic stimulation, and the disruption could be rescued if they were brought back to normal oxygen tension. Cell motility increased with the stimulation by LPS and hypoxia, most probably mediated by the induction of B7-1 and HIF-1 alpha, respectively. We generated a B7-1 knockdown podocyte cell line using the lentiviral small interfering RNA system. The LPS- and hypoxia-induced stress fiber disruption was largely prevented in the B7-1 knockdown podocytes. The increased cell motility by LPS and hypoxia stimulations was also ameliorated in the B7-knockdown podocytes. In summary, we found that both B7-1 and HIF were upregulated by LPS and hypoxic stimulations in podocytes and they interacted with each other. Hypoxia disrupted the abundant stress fibers and increased cell motility. These hypoxia-induced changes were prevented in B7-knockdown podocytes, and they highlighted the importance of B7-1 expression in the hypoxia-related podocyte injuries.