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Cell Mol Life Sci ; 80(5): 125, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37074502

RESUMO

Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI), and experimental work has revealed detailed insight into the inflammatory response in the kidney. T cells and NFκB pathway play an important role in IRI. Therefore, we examined the regulatory role and mechanisms of IkappaB kinase 1 (IKK1) in CD4+T lymphocytes in an experimental model of IRI. IRI was induced in CD4cre and CD4IKK1Δ mice. Compared to control mice, conditional deficiency of IKK1 in CD4+T lymphocyte significantly decreased serum creatinine, blood urea nitrogen (BUN) level, and renal tubular injury score. Mechanistically, lack in IKK1 in CD4+T lymphocytes reduced the ability of CD4 lymphocytes to differentiate into Th1/Th17 cells. Similar to IKK1 gene ablation, pharmacological inhibition of IKK also protected mice from IRI. Together, lymphocyte IKK1 plays a pivotal role in IRI by promoting T cells differentiation into Th1/Th17 and targeting lymphocyte IKK1 may be a novel therapeutic strategy for IRI.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Camundongos , Animais , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Rim/metabolismo , Injúria Renal Aguda/metabolismo , Traumatismo por Reperfusão/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Isquemia/metabolismo , Diferenciação Celular , Reperfusão , Camundongos Endogâmicos C57BL
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