Inhibition of Reticulon-1A–Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis Development

Fan, Ying; Xiao, Wu; Lee, Kyung Hwa; Salem, Fadi; Wen, Jie; He, Li; Zhang, Jing; Yang, Fei; Cheng, Dongsheng; Bao, Huihui; Liu, Yumei; Lin, Fujun; Jiang, Gengru; Guo, Zhiyong; Wang, Niansong; He, John Cijiang

doi:10.1681/asn.2016091001

Cited by 62 publications

(51 citation statements)

References 44 publications

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“…In our previous studies, we identified a novel ER-associated gene, reticulon-1A (RTN1A), which is associated with the progression of kidney diseases such as diabetic nephropathy and HIV-associated nephropathy (HIVAN)[ 16 , 21 ]. Recently, we reported that RTN1A and ER stress are involved in the development of acute kidney injury (AKI) and progression from AKI to CKD [ 22 ]. These findings suggest a critical role of RTN1A in renal tubular cell injury.…”

Section: Introductionmentioning

confidence: 99%

Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy

Fan

Xiao

et al. 2017

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Hyperuricemia contributes to kidney tubular injury and kidney fibrosis. However, the underlying mechanism remains unclear. Here we examined the role of RTN1A, a novel endoplasmic reticulum (ER)-associated protein and ER stress in hyperuricemic nephropathy. We first found the expression of RTN1A and ER stress markers was significantly increased in kidney biopsies of hyperuricemia patients with kidney injury. In a rat model of hyperuricemic nephropathy (HN) established by oral administration of a mixture of adenine and potassium oxonate, increased expression of RTN1A and ER stress was shown in tubular and interstitial compartment of rat kidneys. Treatment of Febuxostat, a new selective inhibitor of xanthine oxidase (XO), not only attenuated renal tubular injury and tubulointerstitial fibrosis, but also reduced uric acid crystals deposition in HN rat kidneys. In vitro, Febuxostat also reduced ER stress and apoptosis in uric acid treated tubular epithelial cells. Our data suggest that RTN1A and ER stress mediate tubular cell injury and kidney fibrosis in HN. Urate-lowering therapy (ULT) with Febuxostat attenuates uric-acid induced ER stress in renal tubular cells and the progression of HN.

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Section: Introductionmentioning

confidence: 99%

Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy

Fan

Xiao

et al. 2017

Oncotarget

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“…For example, large amount of previous studies provided evidence that oxidoreductase activity, membrane, etc. were closely associated with AKI [ 43 - 45 ]. Dagher PC proposed that activation of p53 are major inducers of apoptotic cell death after ischemic renal injury [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of the expression profile of non-coding RNAs involved in ischemia/reperfusion-induced acute kidney injury in mice using RNA sequencing

2017

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Acute kidney injury (AKI) is a common and serious disease characterized by a rapid decline in renal function and has an unacceptably high mortality rate with no effective treatment beyond supportive care. AKI can be induced by many factors such as ischemia/reperfusion (IR), sepsis, and drug-induced nephrotoxicity. However, the molecular mechanisms of AKI are poorly understood. A non-coding RNA (ncRNA) is a RNA molecule that is not translated into a protein. NcRNAs play multiple roles in cellular processes, and mutations or imbalances of these molecules within the body can cause a variety of diseases. Although growing evidence has supported the key role of ncRNAs in AKI, the specific mechanism remains largely unknown. In this study, the second-generation gene sequencing was performed to investigate the expression patterns of ncRNAs, including microRNA (miRNA), long non-coding RNAs, and circular RNAs, in the kidneys of mice subjected to IR-induced AKI. This information will contribute to future research of the mechanism of ncRNAs in the pathogenesis of AKI and facilitate the identification of novel therapeutic targets of ncRNAs.

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“…Compared with vehicletreated animals, TUDCA treatment prior to renal ischemia/ reperfusion results in lower blood urea nitrogen levels and decreased renal histological injury, 39 as well as diminished necrosis and apoptosis. 41 More recent studies report beneficial effects of TUDCA treatment against aldosterone-infused renal injury 42 and diabetic nephropathy. 41 More recent studies report beneficial effects of TUDCA treatment against aldosterone-infused renal injury 42 and diabetic nephropathy.…”

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“…40 Short-term treatment with TUDCA was also recently shown to protect against folic acid nephropathy in a mouse model of the disease. 41 More recent studies report beneficial effects of TUDCA treatment against aldosterone-infused renal injury 42 and diabetic nephropathy. 43,44 In this study, we hypothesized that TUDCA treatment would prevent the development of proteinuria, albuminuria and renal glomerular and/or tubular injury in a model of salt-sensitive hypertension, the ET B -deficient rat.…”

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Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt‐induced renal injury and inflammation

et al. 2018

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Aim: Chronic high salt intake exaggerates renal injury and inflammation, especially with the loss of functional ET B receptors. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and bile salt that is approved for the treatment of hepatic diseases. Our aim was to determine whether TUDCA is reno-protective in a model of ET B receptor deficiency with chronic high salt-induced renal injury and inflammation. Methods: ET B -deficient and transgenic control rats were placed on normal (0.8% NaCl) or high salt (8% NaCl) diet for 3 weeks, receiving TUDCA (400 mg/kg/d; ip) or vehicle. Histological and biochemical markers of kidney injury, renal cell death and renal inflammation were assessed. Results: In ET B -deficient rats, high salt diet significantly increased glomerular and proximal tubular histological injury, proteinuria, albuminuria, excretion of tubular injury markers KIM-1 and NGAL, renal cortical cell death and renal CD4 + T cell numbers. TUDCA treatment increased proximal tubule megalin expression as well as prevented high salt diet-induced glomerular and tubular damage in ET B -deficient rats, as indicated by reduced kidney injury markers, decreased glomerular permeability and proximal tubule brush border restoration, as well as reduced renal inflammation. However, TUDCA had no significant effect on blood pressure. Conclusions: TUDCA protects against the development of glomerular and proximal tubular damage, decreases renal cell death and inflammation in the renal cortex in rats with ET B receptor dysfunction on a chronic high salt diet. These results highlight the potential use of TUDCA as a preventive tool against chronic high salt induced renal damage. K E Y W O R D SCD4 + T cells, cell death, ET B receptors, high salt diet, renal injury

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Inhibition of Reticulon-1A–Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis Development

Cited by 62 publications

References 44 publications

Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy

Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy

Systematic analysis of the expression profile of non-coding RNAs involved in ischemia/reperfusion-induced acute kidney injury in mice using RNA sequencing

Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt‐induced renal injury and inflammation

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