scholarly journals Long non-coding RNA GAS5 aggravate renal epithelial cell apoptosis in cisplatin-induced AKI by regulating miR-205-5p

2021 ◽  
Author(s):  
Min Zhang ◽  
Hui Bi ◽  
Shaoyan Wang ◽  
Xuejuan Sun ◽  
Yinan Li
Keyword(s):  
Epithelial Cells ◽  
Kidney Injury ◽  
Human Kidney ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Promoting Effect ◽  
Renal Epithelial Cell ◽  
Non Coding Rna ◽  
Renal Tubular ◽  
Long Non Coding Rna

Abstract Introduction: The present study focuses on the interaction between long non-coding RNA GAS5 and microRNA-205-5p and their roles in cisplatin-induced acute kidney injury. Methods: Human kidney tubular cells (HK-2) were used to simulate acute renal injury induced by cisplatin with the consequent fluctuating expression levels of GAS5 and MIR-205-5p being determined respectively. Furthermore, the modulating effects of miR-205-5p and GAS5 in cisplatin-induced apoptosis of renal tubular epithelial cells and the possible binding sites between them were evaluated. Results: The results depicted that the expression of GAS5 was significantly up-regulated after AKI induced by cisplatin, while inhibiting the increase of expression would alleviate the apoptotic-promoting effect of cisplatin on renal tubular epithelial cells. MIR-205-5p is negatively regulated by GAS5, thus down-regulation of GAS5 will consequently elevate the expression of miR-205-5p and further alleviate the damage of HK-2 cells induced by cisplatin. Conclusions: In conclusion, in cisplatin-induced AKI, the expression of GAS5 was increased and consequently inhibited that of miR-205-5p by direct binding, which eventually aggravate the renal tubular epithelial injury, indicating their potential of being important diagnostic markers and therapeutic targets in the treatment of cisplatin-induced AKI.

scholarly journals Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Sepsis-Induced Acute Kidney Injury by Promoting Mitophagy of Renal Tubular Epithelial Cells via the SIRT1/Parkin Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Guo ◽  
Rong Wang ◽  
Donghai Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Differentiation Potential ◽  
Renal Tubular

Sepsis is a common risk factor for acute kidney injury (AKI). Bone marrow-derived mesenchymal stem cells (BMSCs) bear multi-directional differentiation potential. This study explored the role of BMSCs in sepsis-induced AKI (SI-AKI). A rat model of SI-AKI was established through cecal ligation and perforation. The SI-AKI rats were injected with CM-DiL-labeled BMSCs, followed by evaluation of pathological injury of kidney tissues and kidney injury-related indicators and inflammatory factors. HK-2 cells were treated with lipopolysaccharide (LPS) to establish SI-SKI model in vitro. Levels of mitochondrial proteins, autophagy-related proteins, NLRP3 inflammasome-related protein, and expressions of Parkin and SIRT1 in renal tubular epithelial cells (RTECs) of kidney tissues and HK-2 cells were detected. The results showed that BMSCs could reach rat kidney tissues and alleviate pathological injury of SI-SKI rats. BMSCs inhibited inflammation and promoted mitophagy of RTECs and HK-2 cells in rats with SI-AKI. BMSCs upregulated expressions of Parkin and SIRT1 in HK-2 cells. Parkin silencing or SIRT1 inhibitor reversed the promoting effect of BMSCs on mitophagy. BMSCs inhibited apoptosis and pyroptosis of RTECs in kidney tissues by upregulating SIRT1/Parkin. In conclusion, BMSCs promoted mitophagy and inhibited apoptosis and pyroptosis of RTECs in kidney tissues by upregulating SIRT1/Parkin, thereby ameliorating SI-AKI.

Effect of Forkhead Box O1 in Renal Tubular Epithelial Cells on Endotoxin-Induced Acute Kidney Injury

2020 ◽  
Author(s):  
Mengxi Zhang ◽  
Wei Dong ◽  
Zhilian Li ◽  
Zhenmeng Xiao ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Mitochondrial Damage ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Forkhead Box ◽  
Renal Tubular

Mitochondrial damage in renal tubular epithelial cells (RTECs) is a hallmark of endotoxin-induced acute kidney injury (AKI). Forkhead box O1 (FOXO1) is responsible for regulating mitochondrial function and is involved in several kidney diseases. Herein, we investigated the effect of FOXO1 on endotoxin-induced AKI and the related mechanism. In vivo, FOXO1 downregulation in mouse RTECs and mitochondrial damage were found in endotoxin-induced AKI. Overexpression of FOXO1 by kidney focal adeno-associated virus (AAV) delivery improved renal function and reduced mitochondrial damage. PGC1-α, a master regulator of mitochondrial biogenesis and function, was reduced in endotoxin-induced AKI, but the reduction was reversed by FOXO1 overexpression. In vitro, exposure to LPS led to a decline in HK-2 cell viability, mitochondrial fragmentation, and mitochondrial superoxide accumulation, as well as downregulation of FOXO1, PGC1-α and mitochondrial complex I/V. Moreover, overexpression of FOXO1 in HK-2 cells increased HK-2 cell viability and PGC1-α expression, and it alleviated the mitochondrial injury and superoxide accumulation induced by LPS. Meanwhile, inhibition of FOXO1 in HK-2 cells by siRNA treatment decreased PGC1-α expression and HK-2 cell viability. Chromatin immunoprecipitation assays and PCR analysis confirmed that FOXO1 bound to the PGC1-α promoter in HK-2 cells. In conclusion, downregulation of FOXO1 in RTECs mediated endotoxin-induced AKI and mitochondrial damage. Overexpression of FOXO1 could improve renal injury and mitochondrial dysfunction, and this effect occurred at least in part as a result of PGC1-α signaling. FOXO1 might be a potential target for the prevention and treatment of endotoxin-induced AKI.

scholarly journals ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jian-kun Deng ◽  
Xueqin Zhang ◽  
Hong-luan Wu ◽  
Yu Gan ◽  
Ling Ye ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Adaptive Response ◽  
Kidney Injury ◽  
Urinary Protein ◽  
Cellular Injury ◽  
Erk Pathway ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Urinary Proteins ◽  
Renal Tubular

ERK, an extracellular signal-regulated protein kinase, is involved in various biological responses, such as cell proliferation and differentiation, cell morphology maintenance, cytoskeletal construction, apoptosis, and canceration of cells. In this study, we focused on ERK pathway on cellular injury and autophagy-associated adaptive response in urinary protein-irritated renal tubular epithelial cells and explored the potential mechanisms underlying it. By using antioxidants N-acetylcysteine and catalase, we found that ERK pathway was activated by a reactive oxygen species- (ROS-) dependent mechanism after exposure to urinary proteins. What is more, ERK inhibitor U0126 could decrease the release of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and the number of apoptotic cells induced by urinary proteins, indicating the damaging effects of ERK pathway in mediating cellular injury and apoptosis in HK-2 cells. Interestingly, we also found that the increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II (a key marker of autophagy) and the decreased expression of p62 (autophagic substrate) induced by urinary proteins were reversed by U0126, suggesting autophagy was activated by ERK pathway. Furthermore, rapamycin reduced urinary protein-induced NGAL and KIM-1 secretion and cell growth inhibition, while chloroquine played the opposite effect, indicating that autophagy activation by ERK pathway was an adaptive response in the exposure to urinary proteins. Taken together, our results indicate that activated ROS-ERK pathway can induce cellular injury and in the meantime provide an autophagy-associated adaptive response in urinary protein-irritated renal tubular epithelial cells.

scholarly journals Upregulation of lncRNA NONRATG019935.2 suppresses the p53-mediated apoptosis of renal tubular epithelial cells in septic acute kidney injury

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Ying Ding ◽  
Dao-yang Zhou ◽  
Hong Yu ◽  
Tao Zhu ◽  
Feng Guo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Epithelial Cells ◽  
Rat Model ◽  
Mrna Stability ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Septic Acute Kidney Injury ◽  
Renal Tubular

AbstractAlthough increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3′UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.

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