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IDH2 gene deficiency accelerates unilateral ureteral obstructioninduced kidney inflammation through oxidative stress and activation of macrophages

Korean Journal of Physiology & Pharmacology 2021년 25권 2호 p.139 ~ 146
김지인, 노미라, 윤가은, 장희성, 공민정, 박권무,
소속 상세정보
김지인 ( Kim Jee-In ) - Keimyung University School of Medicine Department of Molecular Medicine
노미라 ( Noh Mi-Ra ) - Kyungpook National University School of Medicine Department of Anatomy
윤가은 ( Yoon Ga-Eun ) - Keimyung University School of Medicine Department of Molecular Medicine
장희성 ( Jang Hee-Seong ) - Kyungpook National University School of Medicine Department of Anatomy
공민정 ( Kong Min-Jung ) - Kyungpook National University School of Medicine Department of Anatomy
박권무 ( Park Kwon-Moo ) - Kyungpook National University School of Medicine Department of Anatomy

Abstract


Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilateral ureteral obstruction (UUO)-induced kidney inflammation using IDH2 gene deleted mice (IDH2?/?). Eight- to 10-week-old female IDH2?/? mice and wild type (IDH2+/+) littermates were subjected to UUO and kidneys were harvested 5 days after UUO. IDH2 was not detected in the kidneys of IDH2?/? mice, while UUO decreased IDH2 in IDH2+/+ mice. UUO increased the expressions of markers of oxidative stress in both IDH2+/+ and IDH2?/? mice, and these changes were greater in IDH2?/? mice compared to IDH2+/+ mice. Bone marrow-derived macrophages of IDH2?/? mice showed a more migrating phenotype with greater ruffle formation and Rac1 distribution than that of IDH2+/+ mice. Correspondently, UUO-induced infiltration of monocytes/macrophages was greater in IDH2?/? mice compared to IDH2+/+ mice. Taken together, these data demonstrate that IDH2 plays a protective role against UUO-induced inflammation through inhibition of oxidative stress and macrophage infiltration.

키워드

IDH2; Inflammation; Macrophage; Oxidative stress; Ureteral obstruction

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