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      Autophagy and Inflammation Regulation in Acute Kidney Injury

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          Abstract

          Autophagy at an appropriate juncture in the cell cycle exerts protective effects in acute kidney injury (AKI), whereas abnormal autophagy may lead to cell death. Inflammatory response plays a pivotal role in the pathophysiological process of kidney injury and repair during AKI. Several studies have reported an interaction between autophagy and inflammation in the pathogenesis of AKI. This review outlines recent advances in the investigation of the role of autophagy in inflammatory response regulation based on the following aspects. (1) Autophagy inhibits inflammatory responses induced in AKI through the regulation of mTOR and AMPK pathways and the inhibition of inflammasomes activation. (2) Autophagy can also help in the regulation of inflammatory responses through the nuclear factor kappa B pathway, which is beneficial to the recovery of kidney tissues. These studies reviewed here provide better insight into the mechanisms underlying the protective effects of the autophagy-inflammatory pathway. Through this review, we suggest that the autophagy-inflammatory pathway may serve as an alternative target for the treatment of AKI.

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          Most cited references87

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          AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.

          Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.
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            Autophagy: renovation of cells and tissues.

            Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. Copyright © 2011 Elsevier Inc. All rights reserved.
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              The role of Atg proteins in autophagosome formation.

              Macroautophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of cytoplasm for delivery to the lysosome. Autophagosome formation is dynamically regulated by starvation and other stresses and involves complicated membrane reorganization. Since the discovery of yeast Atg-related proteins, autophagosome formation has been dissected at the molecular level. In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                25 September 2020
                2020
                : 11
                : 576463
                Affiliations
                [1] 1Experimental Animal Center, Nanfang Hospital, Southern Medical University , Guangzhou, China
                [2] 2Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University , Zhanjiang, China
                [3] 3School of Health Professions, University of Alabama at Birmingham , Birmingham, AL, United States
                Author notes

                Edited by: Zhanjun Jia, Nanjing Medical University, China

                Reviewed by: Ran You, Nanjing Children’s Hospital, China; Melanie J. Scott, University of Pittsburgh, United States

                *Correspondence: Li Gong, gongli009@ 123456126.com

                These authors share first authorship

                This article was submitted to Renal and Epithelial Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2020.576463
                7546328
                33101057
                5c570d7a-00b1-4e64-8f5e-91824e667986
                Copyright © 2020 Gong, Pan and Yang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 June 2020
                : 25 August 2020
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 87, Pages: 10, Words: 8065
                Funding
                Funded by: Science and Technology Plan Project of the Guangdong Province
                Award ID: 2014A030304024
                Funded by: Science and Technology Plan Project of Zhanjiang City
                Award ID: 2017A01009
                Award ID: 2017A01010
                Categories
                Physiology
                Review

                Anatomy & Physiology
                autophagy,inflammatory,acute kidney injury,immune cells,tubular epithelial cells

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