Role of tubular epithelial arginase-II in renal inflammaging

Abstract 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 accelerati...

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Autores principales:	Ji Huang, Xiujie Liang, Diogo Ladeiras, Benoit Fellay, Xiu-Fen Ming, Zhihong Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/551be1cd250d48858de9a6985292e79c
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spelling	oai:doaj.org-article:551be1cd250d48858de9a6985292e79c2021-12-02T13:30:49ZRole of tubular epithelial arginase-II in renal inflammaging10.1038/s41514-021-00057-82056-3973https://doaj.org/article/551be1cd250d48858de9a6985292e79c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00057-8https://doaj.org/toc/2056-3973Abstract 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.Ji HuangXiujie LiangDiogo LadeirasBenoit FellayXiu-Fen MingZhihong YangNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Ji Huang Xiujie Liang Diogo Ladeiras Benoit Fellay Xiu-Fen Ming Zhihong Yang Role of tubular epithelial arginase-II in renal inflammaging
description	Abstract 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.
format	article
author	Ji Huang Xiujie Liang Diogo Ladeiras Benoit Fellay Xiu-Fen Ming Zhihong Yang
author_facet	Ji Huang Xiujie Liang Diogo Ladeiras Benoit Fellay Xiu-Fen Ming Zhihong Yang
author_sort	Ji Huang
title	Role of tubular epithelial arginase-II in renal inflammaging
title_short	Role of tubular epithelial arginase-II in renal inflammaging
title_full	Role of tubular epithelial arginase-II in renal inflammaging
title_fullStr	Role of tubular epithelial arginase-II in renal inflammaging
title_full_unstemmed	Role of tubular epithelial arginase-II in renal inflammaging
title_sort	role of tubular epithelial arginase-ii in renal inflammaging
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/551be1cd250d48858de9a6985292e79c
work_keys_str_mv	AT jihuang roleoftubularepithelialarginaseiiinrenalinflammaging AT xiujieliang roleoftubularepithelialarginaseiiinrenalinflammaging AT diogoladeiras roleoftubularepithelialarginaseiiinrenalinflammaging AT benoitfellay roleoftubularepithelialarginaseiiinrenalinflammaging AT xiufenming roleoftubularepithelialarginaseiiinrenalinflammaging AT zhihongyang roleoftubularepithelialarginaseiiinrenalinflammaging
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Role of tubular epithelial arginase-II in renal inflammaging

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