Dataset Information

The role of nuclear factor erythroid-2-related factor 2 expression in radiocontrast-induced nephropathy.

ABSTRACT: Radiocontrast-induced nephropathy (CIN) is the third most common cause of acute renal failure. The pathophysiology of CIN is related to tubular injury caused by oxidative stress, and nuclear factor erythroid-2-related factor 2 (Nrf2) is critical in coordinating intracellular antioxidative processes. We thus investigated the role of Nrf2 in CIN. CIN was established in mice and in NRK-52E cells via iohexol administration according to the protocols of previous studies. To determine the role of Nrf2 in CIN, Nrf2 expression was reduced in vivo using Nrf2 knockout (KO) mice (B6.129 × 1-Nfe2 l2tm1Ywk/J) and in vitro with siRNA treatment targeting Nrf2. Increased Nrf2 expression was observed after iohexol treatment both in vivo and in vitro. Serum creatinine at 24 h after iohexol injection was significantly higher in KO mice than in wild-type (WT) mice. Histologic examination showed that iohexol-induced tubular vacuolization and structural disruption were aggravated in Nrf2 KO mice. Significant increases in apoptosis and F4/80(+) inflammatory cell infiltration were demonstrated in KO mice compared to WT mice. In addition, the increase in reactive oxygen species after iohexol treatment was augmented by Nrf2 inhibition both in vivo and in vitro. Nrf2 may be implicated in the pathogenesis of CIN via the modulation of antioxidant, anti-apoptotic, and anti-inflammatory processes.

SUBMITTER: Kim JE

PROVIDER: S-EPMC6384919 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The pathogenesis of respiratory syncytial virus (RSV) infections is characterized by lower airway obstruction driven at great extent by the exuberant production of inflammatory cytokines. We have previously shown that RSV infection in vitro and in vivo results in production of reactive oxygen species along with reduction in the expression of antioxidant enzymes (AOEs), which are involved in maintaining the cellular oxidant-antioxidant balance. These events were associated with the concomitant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that controls AOE expression. The objective of the current study was to establish the role of Nrf2 in shaping innate immune responses, clinical disease, airway inflammation, and viral replication in established experimental models of intranasal RSV and human metapneumovirus (hMPV) infections, by employing mice genetically deficient for the Nrf2 gene. Compared to control wild type (WT), mice genetically deficient in Nrf2 (Nrf2 KO) developed enhanced clinical disease, airway inflammation and pathology, and significantly greater lung viral titers following experimental infection with either RSV or hMPV. In particular, compared to control mice, RSV-infected Nrf2 KO mice lost more body weight and had increased airway obstruction at time points characterized by a remarkable increase in inflammatory cytokines and airway neutrophilia. Airway levels of AOEs and enzymes that regulate synthesis of the endogenous hydrogen sulfide (H2S) pathway, which we showed to play an important antiviral function, were also decreased in RSV-infected Nrf2 KO compared to WT. In conclusion, these results suggest that Nrf2 is a critical regulator of innate, inflammatory, and disease-associated responses in the airways of mice infected with viruses that are members of the Pneumoviridae family. Importantly, the results of this study suggest that Nrf2-dependent genes, including those controlling the cellular antioxidant and H2S-generating enzymes and cytokines can affect several aspects of the antiviral response, such as airway neutrophilia, clinical disease, airway obstruction, and viral replication.

Dataset Information

The role of nuclear factor erythroid-2-related factor 2 expression in radiocontrast-induced nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure