Activation of autophagy contributes to the renoprotective effect of postconditioning on acute kidney injury and renal fibrosis

Song, Yanqing; Tao, Qianyu; Liu, Yu; Li, Ling; Bai, Tingting; Song, Xiaoxiao; Hu, Haiqi; Li, Yulin; Tan, Xiaohua

doi:10.1016/j.bbrc.2018.09.003

Cited by 30 publications

(21 citation statements)

References 29 publications

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“…Elafibranor, a novel dual peroxisome proliferator-activator receptor α/δ (PPARα/δ) agonist, protected HFD mice with CKD by improving kidney-specific protective effects, including preservation of glomerular/tubular barrier protein, maintenance of the structure, antioxidative stress, and activation of sirtuin (SIRT)-autophagy [56]. Postconditioning (POC) following IR injury reduced renal damage and renal fibrosis by increased autophagy [57]. Periostin gene, also known as osteoblast-specific factor-2 that plays a role as a profibrotic and proinflammatory factor [58], is upregulated in kidneys with 5-6 nephrectomy and impaired autophagy flux.…”

Section: Autophagy In Renal Interstitial Fibrosis and Progressive Kidmentioning

confidence: 99%

Autophagy Function and Regulation in Kidney Disease

et al. 2020

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Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

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Section: Autophagy In Renal Interstitial Fibrosis and Progressive Kidmentioning

confidence: 99%

Autophagy Function and Regulation in Kidney Disease

et al. 2020

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“…A large number of studies show that renal tubular epithelial cells undergoing apoptosis can promote the development of renal dysfunction in ischemia-reperfusion (I/R) and septic AKI model (Lerolle et al, 2010). Autophagy is activated to prevent renal dysfunction from injury (Song et al, 2018). Studies have shown that renal tubular epithelium is the main site of oxidative stress, and reactive oxygen species (ROS) and reactive nitrogen (RNS) play important roles in acute renal tubular injury during sepsis (Pathak et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic Blockade of 15-PGDH Protects Against Acute Renal Injury Induced by LPS in Mice

Miao

Liu

et al. 2020

Front. Physiol.

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Prostaglandin pathway plays multiple roles in various physiological and pathological conditions. The present study aimed to investigate the effect of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in the degradation of prostaglandins, on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice. In this study, male C57BL/6J mice were injected intraperitoneally with LPS (10 mg/kg). SW033291, a potent small-molecule inhibitor of 15-PGDH, was used to investigate the therapeutic potential of 15-PGDH inhibition on LPS-induced AKI. We discovered that the expression of 15-PGDH protein was upregulated in kidneys of LPS-stimulated mice, and it was mainly localized in the cytoplasm of renal tubular epithelial cells in renal cortex and outer medulla. SW033291 administration improved the survival rates of mice and attenuated renal injury of mice that were challenged by LPS. Additionally, inhibition of 15-PGDH also reversed LPS-induced apoptosis of renal cells, increased expression of anti-apoptotic protein Bcl-2, and downregulated expression of Fas, caspase-3, and caspase-8. Pretreatment of SW033291 enhanced autophagy in kidney cells after LPS stimulation. Our data also showed that inhibition of 15-PGDH relieved the level of lipid peroxidation and downregulated NADPH oxidase subunits induced by LPS in mice kidneys but had no significant effect on the release of inflammatory factors, such as IL-6, IL-1β, TNF-α, and MCP-1. Our study demonstrated that inhibition of 15-PGDH could alleviate LPS-induced AKI by regulating the apoptosis, autophagy, and oxidative stress rather than inflammation in mice.

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“…In recent years, mounting evidence has proved that autophagy is involved in the development of kidney disease, especially in renal fibrosis [34]. However, whether autophagy activation protects renal cells from injury remains controversial [9,35]. It is reported that autophagy activation protects renal cells from injury induced by aristolochic acid, cisplatin, or cyclosporine A [36][37][38].…”

Section: 0mentioning

confidence: 99%

“…Accumulating evidence indicates that fibrotic and apoptotic responses play significant roles in CKD progression and development [5][6][7]. Autophagy activation is reported to have protective effects against diverse renal cell injuries, such as hypoxia, ischemia/reperfusion, oxidative stress, and endstage renal fibrosis [8][9][10]. In addition, proteinuria, as a damaging factor, can result in renal tubular atrophy and interstitial fibrosis [11,12].…”

Section: Introductionmentioning

confidence: 99%

Yiqihuoxue Formula Activates Autophagy and Offers Renoprotection in a Rat Model of Adenine-Induced Kidney Disease

Xia

Xue

Zhang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Chronic kidney disease (CKD) is a worldwide health problem for which effective therapeutic methods are still lacking. Traditional Chinese medicine (TCM) has been indicated as an effective alternative treatment for kidney disease. In this study, a clinically effective therapy, yiqihuoxue (YQHX) formula, was administrated to adenine-induced kidney disease rats for 6 weeks. We found that the adenine rats displayed a significant reduction in renal function as evidenced by the increased levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24-h urinary albumin level, which were attenuated by the YQHX treatment. The glomerulosclerosis, interstitial fibrosis, arteriolosclerosis, interstitial inflammation, and tubular dilatation were reversed by the YQHX treatment in the adenine rats. Furthermore, the hepatic damage characterized by increased levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cell infiltration was improved by YQHX. In addition, the number of apoptotic cells in the adenine rats was obviously reduced by the YQHX treatment as manifested by the lower expression level of cleaved caspase-3 protein. Moreover, the YQHX treatment downregulated the expression levels of fibronectin, type I collagen, α-smooth muscle actin, and TGF-β1 in the adenine rats. Furthermore, autophagy was activated by the YQHX treatment, which manifested as an increased LC3-II and Beclin-1 expression levels and a decreased p62 level. In conclusion, the YQHX formula might retard the progression of kidney disease by activating autophagy.

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Activation of autophagy contributes to the renoprotective effect of postconditioning on acute kidney injury and renal fibrosis

Cited by 30 publications

References 29 publications

Autophagy Function and Regulation in Kidney Disease

Autophagy Function and Regulation in Kidney Disease

Pharmacologic Blockade of 15-PGDH Protects Against Acute Renal Injury Induced by LPS in Mice

Yiqihuoxue Formula Activates Autophagy and Offers Renoprotection in a Rat Model of Adenine-Induced Kidney Disease

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