Synergistic effect of hypoxia and TNF-α on production of PAI-1 in human proximal renal tubular cells

Abstract

Hypoxia induces PAI-1 expression via remarkable nuclear accumulation of HIF-1alpha and partially via NF-kappaB activation in HPTECs. TNF-alpha can synergistically enhance this hypoxia-induced PAI-1 expression.

Prolyl hydroxylase-1 negatively regulates IκB kinase-β, giving insight into hypoxia-induced NFκB activity

“…This has important implications in cancer where elevated levels of proinflammatory cytokines coexist with hypoxia in the microenvironment of the tumor (33). Furthermore, this is consistent with previous studies demonstrating synergy between hypoxia and inflammatory cytokines in the activation of cells (10,34).…”

Hypoxia Induces Permeability and Giant Cell Responses of Andes Virus-Infected Pulmonary Endothelial Cells by Activating the mTOR-S6K Signaling Pathway

“…Hypoxia increases endothelial NO synthase (eNOS), which is responsible for lymphatic vessel contraction and fluid clearance functions (101,102). Although tumor necrosis factor alpha (TNF-␣) alone does not permeabilize hantavirus-infected cells (103), hypoxia also synergistically induces VEGF in response to transforming growth factor ␤ (TGF-␤) or TNF-␣ stimulation, suggesting a potential role for these factors under hypoxic conditions in vivo (104). Prolonged hypoxia also impairs active sodium transport across the alveolar epithelium by inhibiting the Na ϩ -K ϩ -ATPase and directing ubiquitin proteasome-directed degradation of the Na ϩ pump (72).…”

Connexin 32 as an Anti-invasive and Anti-metastatic Gene in Renal Cell Carcinoma

“…34) A key event of hypoxia adaptation in tumor cells is to induce hypoxia-inducible factor (HIF) via the activation of Src, because HIF acts as a potential inducer of genes required for invasion and metastasis under hypoxia including PAI-1 and VEGF. 35,36) As mentioned, we have reported that Cx32 reduced productions of PAI-1 and VEGF in metastatic RCC cells via the inhibition of Src signaling. Taken together, it seems that inhibition of hypoxic adaptation of metastatic RCC cells is critical for anti-invasive anti-metastatic effects of Cx32 (Fig.…”