title: B7-1 expression regulates the hypoxia-driven cytoskeleton rearrangement in glomerular podocytes.
abstract: 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)-1α expression in podocytes. B7-1, an essential player in the regulation of podocyte stress fibers, interacted directly with the NH(2)-terminal oxygenation domain of HIF-1α 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-1α, 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.
authors.affiliation: Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kango Hospital, Kaohsiung, Taiwan.
authors.forename: Jer-Ming
authors.initials: JM
authors.lastname: Chang
authors.forename: Daw-Yang
authors.initials: DY
authors.lastname: Hwang
authors.forename: Szu-Chia
authors.initials: SC
authors.lastname: Chen
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Kuo
authors.forename: Chi-Chih
authors.initials: CC
authors.lastname: Hung
authors.forename: Shang-Jyh
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Jer-Chia
authors.initials: JC
authors.lastname: Tsai
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis*; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D050199:Podocytes / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D018122:B7-1 Antigen; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse