scholarly journals Assessing the recovery from prerenal and renal acute kidney injury after treatment with single herbal medicine via activity of the biomarkers HMGB1, NGAL and KIM-1 in kidney proximal tubular cells treated by cisplatin with different doses and exposure times

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Sung-Man Oh ◽  
Gunhyuk Park ◽  
Seung Hoon Lee ◽  
Chang-Seob Seo ◽  
Hyeun-Kyoo Shin ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Herbal Medicine ◽  
Kidney Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Kidney Proximal Tubular Cells ◽  
Different Doses

scholarly journals Canagliflozin protects against cisplatin-induced acute kidney injury by AMPK-mediated autophagy in renal proximal tubular cells

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Cheol Ho Park ◽  
Bin Lee ◽  
Myeonggil Han ◽  
Woo Joong Rhee ◽  
Man Sup Kwak ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Kidney Injury ◽  
Proximal Tubular Cells ◽  
Cell Viability Assay ◽  
Tubular Cells ◽  
Compound C ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

AbstractSodium-glucose cotransporter 2 inhibitors, which are recently introduced as glucose-lowering agents, improve cardiovascular and renal outcomes in patients with diabetes mellitus. These drugs also have beneficial effects in various kidney disease models. However, the effect of SGLT2 inhibitors on cisplatin-induced acute kidney injury (AKI) and their mechanism of action need to be elucidated. In this study, we investigated whether canagliflozin protects against cisplatin-induced AKI, depending on adenosine monophosphate-activated protein kinase (AMPK) activation and following induction of autophagy. In the experiments using the HK-2 cell line, cell viability assay and molecular analysis revealed that canagliflozin protected renal proximal tubular cells from cisplatin, whereas addition of chloroquine or compound C abolished the protective effect of canagliflozin. In the mouse model of cisplatin-induced AKI, canagliflozin protected mice from cisplatin-induced AKI. However, treatment with chloroquine or compound C in addition to administration of cisplatin and canagliflozin eliminated the protective effect of canagliflozin. Collectively, these findings indicate that canagliflozin protects against cisplatin-induced AKI by activating AMPK and autophagy in renal proximal tubular cells.

scholarly journals The exosomes derived from urine of premature infants target MAPK8 via miR-30a-5p to protect cisplatin-induced acute kidney injury in mice

2021 ◽  
Author(s):  
Mingming Ma ◽  
Qiao Luo ◽  
Lijing Fan ◽  
Weilong Li ◽  
Qiang Li ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Premature Infants ◽  
Target Genes ◽  
Kidney Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Hk2 Cells

Aim: Acute kidney injury (AKI), a global public health issue, not only causes millions of deaths every year, but is also a susceptible factor for chronic kidney disease (CKD). Nephrotoxic drugs are an important cause of AKI. There is still a lack of effective and satisfactory prevention method in clinical practice. This study investigated the protective effect of the exosomes derived from urine of premature infants on cisplatin-induced acute kidney injury. Methods: Isolation of exosomes from fresh urine of premature infants: The characteristics of exosomes were determined by flow cytometry, transmission electron microscopy and Western blotting. A C57BL/6 mice model of cisplatin-induced acute kidney injury was established. The mice in the experimental group were given 100ug exosomes dissolved in 200ul solution. The mice in the control group were given normal saline (200ul). These treatments were performed 24 hours after AKI was induced by intraperitoneal injection of cisplatin. To evaluate renal function, blood was drawn 24 hours after AKI model was established and serum creatinine (sCr) was measured. The mice were euthanized 72 hours after exosome treatment. The kidneys were collected for pathological examination, RNA and protein extraction, and the evaluation of renal tubular damage and apoptosis. In the in-vitro experiment, human renal cortex/proximal tubular cells (HK2) was induced by cisplatin to assess the protective ability of the exosomes derived from urine of premature infants. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blotting were used to evaluate the effect of exosomes treatment on the apoptosis of HK2 cells induced by cisplatin. Exosome microRNA sequencing technology and bioinformatics analysis method were applied to investigate the miRNAs enriched in exosomes and their target genes. The dual luciferase gene reporter system was used to detect the interaction of target genes. Results: Treatment of exosomes derived from urine of premature infants could decrease the level of serum creatinine and the apoptosis of renal tubular cell, inhibit the infiltration of inflammatory cell, protect mice from acute kidney injury induced by cisplatin and reduce mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes derived from urine of premature infants. It protected HK2 cells from cisplatin-induced apoptosis by targeting and down-regulating the 3'UTR of mitogen-activated protein kinases (MAPK8) mRNA. Conclusions: According to our results, the exosomes derived from urine of premature infants alleviated cisplatin-induced acute kidney injury in mice and inhibited the apoptosis of human proximal tubular cells (HK2) induced by cisplatin in vitro. MiR-30a-5p in exosomes inhibited cisplatin-induced MAPK activation, ameliorated apoptosis, and protected renal function. The exosomes derived from urine of premature infants provided a promising acellular therapy for AKI.

scholarly journals Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 434 ◽  
Author(s):  
Yung-Ho Hsu ◽  
I-Jen Chiu ◽  
Yuh-Feng Lin ◽  
Yi-Jie Chen ◽  
Yu-Hsuan Lee ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Fibrosis ◽  
Kidney Injury ◽  
Human Kidney ◽  
Degradation Pathway ◽  
Acute Stage ◽  
Mrna Levels ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Kidney Proximal Tubular Cells

Patients with acute kidney injury (AKI) who survive the acute stage are at notable risk for chronic kidney disease (CKD) progression. There is no single therapy that can effectively prevent the AKI to CKD transition. Autophagy is a cytoplasmic component degradation pathway and has complex functions in several diseases, such as renal fibrosis. Previous research has shown that lactoferrin has important functions in antioxidant defense and other defense systems, protecting kidneys against various injuries. The present study investigated the effect of lactoferrin in protecting against the AKI to CKD transition. We identified 62 consensus genes with two-fold changes in clinical kidney tissues from AKI and CKD patients. Among the 62 overlay genes, the mRNA levels of LTF were significantly upregulated in the kidney tissues of AKI and CKD patients. Lactoferrin induced autophagy via the activation of the AMPK and inhibition of Akt/mTOR pathway in human kidney proximal tubular cells. Lactoferrin suppressed oxidative stress-induced cell death and apoptosis by augmenting autophagy. Lactoferrin has an antifibrotic role in human kidney tubular cells. In a mouse model of folic acid-induced AKI to CKD transition, treatment with lactoferrin recovered renal function and further suppressed renal fibrosis through the inhibition of apoptosis and the induction of autophagy. These findings identify lactoferrin as a potential therapeutic target for the prevention of the AKI to CKD transition.

scholarly journals miR-214 represses mitofusin-2 to promote renal tubular apoptosis in ischemic acute kidney injury

2020 ◽  
Vol 318 (4) ◽  
pp. F878-F887 ◽  
Author(s):  
Yu Yan ◽  
Zhengwei Ma ◽  
Jiefu Zhu ◽  
Mengru Zeng ◽  
Hong Liu ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Kidney Injury ◽  
Atp Depletion ◽  
Mitochondrial Fragmentation ◽  
Proximal Tubular Cells ◽  
Mitofusin 2 ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Kidney Proximal Tubular Cells

Disruption of mitochondrial dynamics is an important pathogenic event in both acute and chronic kidney diseases, but the underlying mechanism remains poorly understood. Here, we report the regulation of mitofusin-2 (Mfn2; a key mitochondrial fusion protein) by microRNA-214 (miR-214) in renal ischemia-reperfusion that contributes to mitochondrial fragmentation, renal tubular cell death, and ischemic acute kidney injury (AKI). miR-214 was induced, whereas Mfn2 expression was decreased, in mouse ischemic AKI and cultured rat kidney proximal tubular cells (RPTCs) following ATP depletion treatment. Overexpression of miR-214 decreased Mfn2. Conversely, inhibition of miR-214 with anti-miR-214 prevented Mfn2 downregulation in RPTCs following ATP depletion. Anti-miR-214 further ameliorated mitochondrial fragmentation and apoptosis, whereas overexpression of miR-214 increased apoptosis, in ATP-depleted RPTCs. To test regulation in vivo, we established a mouse model with miR-214 specifically deleted from kidney proximal tubular cells (PT- miR-214−/−). Compared with wild-type mice, PT- miR-214−/− mice had less severe tissue damage, fewer apoptotic cells, and better renal function after ischemic AKI. miR-214 induction in ischemic AKI was suppressed in PT- miR-214−/− mice, accompanied by partial preservation of Mfn2 in kidneys. These results unveil the miR-214/Mfn2 axis that contributes to the disruption of mitochondrial dynamics and tubular cell death in ischemic AKI, offering new therapeutic targets.

scholarly journals Reciprocal regulation between ER stress and autophagy in renal tubular fibrosis and apoptosis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Shaoqun Shu ◽  
Hui Wang ◽  
Jiefu Zhu ◽  
Zhiwen Liu ◽  
Danyi Yang ◽  
...  
Keyword(s):  
Er Stress ◽  
Kidney Injury ◽  
Proximal Tubular Cells ◽  
Reciprocal Regulation ◽  
Tubular Cells ◽  
Chronic Kidney Injury ◽  
Proximal Tubular ◽  
Kidney Proximal Tubular Cells ◽  
Tgf Β1

AbstractBoth endoplasmic reticulum (ER) stress and autophagy have been implicated in chronic kidney injury and renal fibrosis. However, the relationship and regulatory mechanisms between ER stress and autophagy under this condition remain largely unknown. In this study, we first established a mouse model of ER stress-induced chronic kidney injury by 2 weekly injections of a low dose of tunicamycin (TM), a classical ER stress inducer. This model showed the induction of ER stress, autophagy, fibrosis and apoptosis in kidney tissues. In vitro, TM also induced ER stress, autophagy, fibrosis and apoptosis in HK-2 human kidney proximal tubular cells and BUMPT-306 mouse kidney proximal tubular cells. In these cells, autophagy inhibitor suppressed TM-induced fibrotic changes and apoptosis, suggesting an involvement of autophagy in ER stress-associated chronic kidney injury. PERK inhibitor ameliorated autophagy, fibrotic protein expression and apoptosis in TM-treated cells, indicating a role of the PERK/eIF2α pathway in autophagy activation during ER stress. Similar results were shown in TGF-β1-treated HK-2 cells. Interestingly, in both TM- or TGF-β1-treated kidney proximal tubular cells, inhibition of autophagy exaggerated ER stress, suggesting that autophagy induced by ER stress provides a negative feedback mechanism to reduce the stress. Together, these results unveil a reciprocal regulation between ER stress and autophagy in chronic kidney injury and fibrosis.

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