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Role of tubular epithelial arginase-II in renal inflammaging
npj Aging and Mechanisms of Disease Pub Date : 2021-03-02 , DOI: 10.1038/s41514-021-00057-8
Ji Huang , Xiujie Liang , Diogo Ladeiras , Benoit Fellay , Xiu-Fen Ming , Zhihong Yang

The aging kidney undergoes complex changes and is vulnerable to injury and development of chronic kidney disease (CKD) with preponderance affecting more women than men. Evidence has been presented that the type-II L-arginine:ureohydrolase, arginase-II (Arg-II) plays a role in the acceleration of aging. Arg-II is highly expressed in the kidney. However, the role of Arg-II in renal aging is not known. This study is to investigate whether Arg-II is involved in the kidney aging process dependently on sex. Arg-II level in the kidney of wild type (WT) mice is significantly elevated with aging, which is accompanied by an increase in expression of the inflammatory cytokines/chemokines, tissue macrophages, factors involved in fibrosis, and tubulointestitial fibrosis in both males and females. This renal aging phenotype is significantly suppressed in arg-II−/− mice, mainly in the females in which Arg-II level is higher than in the males. Importantly, numerous factors such as IL-1β, MCP1, VCAM-1, and TGFβ1 are mainly localized in the proximal tubular S3 segment cells expressing Arg-II in the aging kidney. In human proximal tubular cells (HK-2), TNF-α enhances adhesion molecule expression dependently on Arg-II upregulation. Overexpression of Arg-II in the cells enhances TGFβ1 levels which is prevented by mitochondrial ROS inhibition. In summary, our study reveals that renal proximal tubular Arg-II plays an important role in the kidney aging process in females. Arg-II could be a promising therapeutic target for the treatment and prevention of aging-associated kidney diseases.



中文翻译:

肾小管上皮精氨酸酶II的作用

衰老的肾脏会经历复杂的变化,容易受到慢性肾脏病(CKD)的伤害和发展,其优势是女性比男性多。已有证据表明,II型L-精氨酸:脲水解酶,精氨酸酶II(Arg-II)在加速衰老中起作用。Arg-II在肾脏中高度表达。但是,Arg-II在肾衰老中的作用尚不清楚。这项研究旨在调查Arg-II是否依赖于性别参与肾脏衰老过程。随着年龄的增长,野生型(WT)小鼠肾脏中的Arg-II水平显着升高,并伴随着炎症细胞因子/趋化因子,组织巨噬细胞,涉及纤维化的因子和肾小管肠纤维化的表达增加。女性。这种肾衰老表型被显着抑制。arg-II -/-小鼠,主要在其中Arg-II水平高于雄性的雌性中。重要的是,诸如IL-1β,MCP1,VCAM-1和TGFβ1的许多因子主要位于衰老的肾脏中表达Arg-II的近端肾小管S3节段细胞中。在人类近端肾小管细胞(HK-2)中,TNF-α依赖于Arg-II上调增强粘附分子的表达。细胞中Arg-II的过表达增强了TGFβ1的水平,这可通过线粒体ROS抑制来阻止。总而言之,我们的研究表明,肾近端肾小管Arg-II在女性肾脏衰老过程中起着重要作用。Arg-II可能是治疗和预防与衰老相关的肾脏疾病的有希望的治疗靶标。

更新日期:2021-03-02
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