Autophagy activation reduces renal tubular injury induced by urinary proteins

Liu, Wei Jing; Luo, Mian‐Na; Tan, Jin; Chen, Wei; Huang, Lei-zhao; Yang, Chen; Pan, Qingjun; Li, Benyi; Liu, Huafeng

doi:10.4161/auto.27004

Cited by 78 publications

(89 citation statements)

References 42 publications

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“…For example, autophagy activation reduces urinary protein-induced renal tubular injury [20]. Jiang et al [4 ]demonstrated that autophagy in proximal tubules protects against AKI.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury

Liu

Hong²,

Wang³

et al. 2015

Am J Nephrol

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Background: Acute kidney injury (AKI) is traditionally described as a condition leading to rapid damage to kidney function, eventually becoming a significant healthcare concern with a high mortality rate. Autophagy deficiency in the tubular epithelial cells is the main cause of AKI; however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNAs) are related to autophagy in many diseases. This study was aimed at investigating the relationship between miRNA expression and autophagic activity in the pathogenesis of AKI. Methods: A mouse model of AKI was produced by ischemia reperfusion (I/R). The expressions of microRNA-34a (miR-34a) and the autophagy-related protein LC3 II/I and p62 were determined in renal tissues and the tubular epithelial cells (RTECs). Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. Additionally, the effect of miR-34a on its target gene in regulating autophagic activity in RTECs was also investigated. Results: I/R suppressed the autophagic activity and increased the expression of miR-34a in renal tissues. The in vitro data showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in RTECs. Moreover, miR-34a could directly bind to Atg4B 3′-untranslated region. In addition, the knockdown of Atg4B expression inhibited the autophagic activity in RTECs. Conclusion: This study indicated that miR-34a might regulate the autophagic activity and can cause injury in I/R RTECs via targeting Atg4B.

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“…For example, autophagy activation reduces urinary protein-induced renal tubular injury [20]. Jiang et al [4 ]demonstrated that autophagy in proximal tubules protects against AKI.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury

Liu

Hong²,

Wang³

et al. 2015

Am J Nephrol

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“…The rats were randomly divided into four groups (eight rats/group): untreated control group, stone model group, stone model treatment with rapamycin group, and stone model treatment with chloroquine group. Rats in the stone model+Rapa group and stone model+CQ group were intraperitoneally injected with rapamycin (0.25 mg/kg/d) and chloroquine (60 mg/kg/d) , respectively [16]. …”

Section: Methodsmentioning

confidence: 99%

Inhibition of Autophagy Attenuated Ethylene Glycol Induced Crystals Deposition and Renal Injury in a Rat Model of Nephrolithiasis

Liu

Xiang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Nephrolithiasis is a common and frequently occurring disease, its exact pathogenesis is remains unclear. Emerging data suggest that autophagy plays a vital role in the pathophysiological processes of kidney diseases. Therefore, this study was designed to investigate the potential role of autophagy in the formation of calcium oxalate (CaOx) kidney stones in rat model. Methods: Thirty-two rats were randomly divided into four groups (eight rats/group): untreated control group, stone model group, rapamycin-treated group, chloroquine-treated group. Rat models of CaOx nephrolithiasis was administration of 0.75% ethylene glycol (EG) in their drinking water for 4 weeks. Western blot and transmission electron microscope (TEM) were used to detect the expression of autophagy related protein LC3-II, BECN1 and p62 and autophagic vacuoles respectively. Renal function was evaluated by measuring the levels of serum CRE and BUN. Renal tubular injury markers NGAL and Kim-1 was determined by ELISA kits. Von Kossa staining was used to assess crystal deposits and histological tissue injury. TUNEL staining was employed to assess apoptosis of the renal tubular cell. Results: Compare with the controls, the expression of autophagy related protein LC3-II, BECN1 and number of autophagic vacuoles were increased significantly, whereas the p62 protein level was decreased in the stone model group. The levels of apoptosis, serum CRE and BUN, NGAL and Kim-1 in the stone model group were increased compared with the control group and crystals deposition and renal injury were increased significantly. However, the levels of autophagy, kidney injury and crystal deposition were decreased by chloroquine but increased by rapamycin. Conclusion: These findings suggested that rats were administration of ethylene glycol could lead to the formation of CaOx nephrolithiasis and autophagy activation. Inhibiting autophagy could be an effective therapeutic approach for decreasing the formation of nephrolithiasis.

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“…According to previous studies, we used 2.5 mg/ml BSA treatment as a control for 0.25 mM PA treatment because it has been reported that, at a higher concentration, FA-free BSA has several cytotoxic effects, including ROS production, mitochondrial damage, and endoplasmic reticulum stress, 57,58 all of which could induce autophagy and apoptosis in the PTCs. 59 To assess autophagic activity, PTCs were treated with 200 nM of bafilomycin A1 (Wako) for 1 hour at 37°C before harvest.…”

Section: Cell Culturementioning

confidence: 99%

High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney

Yamamoto¹,

Takabatake²,

Takahashi³

et al. 2016

JASN

176

160

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Excessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation. Pulse-chase experiments revealed that the accumulated lipids originated from cellular membranes. In mice with induced PTC-specific ablation of autophagy, PTCs of HFD-mice exhibited greater accumulation of ubiquitin-positive protein aggregates normally removed by autophagy than did PTCs of mice fed a normal diet. Furthermore, HFD-mice had no capacity to augment autophagic activity upon another pathologic stress. Autophagy ablation also exaggerated HFD-induced mitochondrial dysfunction and inflammasome activation. Moreover, renal ischemia-reperfusion induced greater injury in HFD-mice than in mice fed a normal diet, and ablation of autophagy further exacerbated this effect. Finally, we detected similarly enhanced phospholipid accumulation in enlarged lysosomes and impaired autophagic flux in the kidneys of obese patients compared with nonobese patients. These findings provide key insights regarding the pathophysiology of lipotoxicity in the kidney and clues to a novel treatment for obesity-related kidney diseases.

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Autophagy activation reduces renal tubular injury induced by urinary proteins

Cited by 78 publications

References 42 publications

MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury

MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury

Inhibition of Autophagy Attenuated Ethylene Glycol Induced Crystals Deposition and Renal Injury in a Rat Model of Nephrolithiasis

High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney

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