scholarly journals Long non-coding RNA TUG1 knockdown promotes autophagy and improves acute renal injury in ischemia-reperfusion-treated rats by binding to microRNA-29 to silence PTEN

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhiquan Xu ◽  
Xiaoyan Huang ◽  
Qiuyu Lin ◽  
Wei Xiang
Keyword(s):  
Renal Injury ◽  
Noncoding Rna ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Pten Expression ◽  
Acute Renal Injury ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Abstract Objective Long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) is increased under the condition of ischemia. This study intended to identify the mechanism of TUG1 in renal ischemia-reperfusion (I/R). Methods First, a rat model of acute renal injury induced by I/R was established, followed by the measurement of blood urea nitrogen (BUN), serum creatine (SCr), methylenedioxyphetamine (MDA) and superoxide dismutase (SOD) in the serum of rats. TUG1 was knocked down in I/R rats (ko-TUG1 group). Next, histological staining was used to evaluate the pathological damage and apoptosis of rat kidney. Western blot analysis was used to detect the levels of apoptosis- and autophagy-related proteins and transmission electron microscope was used to observe autophagosomes. Autophagy and apoptosis were evaluated after inhibition of the autophagy pathway using the inhibitor 3-MA. The targeting relation among TUG1, microRNA (miR)-29 and phosphatase and tensin homolog (PTEN) were validated. Lastly, the effects of TUG1 on biological behaviors of renal tubular cells were evaluated in vitro. Results In vivo, the levels of BUN, SCr and MDA in the serum of I/R-treated rats were increased while SOD level and autophagosomes were reduced, tubule epithelial cells were necrotic, and TUG1 was upregulated in renal tissues of I/R-treated rats, which were all reversed in rats in the ko-TUG1 group. Autophagy inhibition (ko-TUG1 + 3-MA group) averted the protective effect of TUG1 knockdown on I/R-treated rats. TUG1 could competitively bind to miR-29 to promote PTEN expression. In vitro, silencing TUG1 (sh-TUG1 group) promoted viability and autophagy of renal tubular cells and inhibited apoptosis. Conclusions LncRNA TUG can promote PTEN expression by competitively binding to miR-29 to promote autophagy and inhibited apoptosis, thus aggravating acute renal injury in I/R-treated rats.

scholarly journals Long non-coding RNA TUG1/microRNA-29/PTEN axis in ischemia-reperfusion in a rat model

2020 ◽  
Author(s):  
Zhiquan Xu ◽  
Xiaoyan Huang ◽  
Qiuyu Lin ◽  
Wei Xiang
Keyword(s):  
Rat Model ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Acute Renal Injury ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Non Coding Rna ◽  
Renal Tubular ◽  
Long Non Coding Rna

Abstract Objective: Long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) is increased under ischemia. This study intended to identify the potential competing endogenous RNA network involving TUG1 in renal ischemia-reperfusion (I/R).Methods: A rat model of acute renal injury induced by I/R was established, and the differentially expressed genes were analyzed by microarray. The levels of blood urea nitrogen (BUN), serum creatine (SCr), methylenedioxyphetamine (MDA) and superoxide dismutase (SOD) in serum of rats were measured. HE staining evaluated the pathological damage of renal tissues, western blot analysis detect the levels of apoptosis- and autophagy-related proteins, immunofluorescence staining detected LC3 fluorescence intensity, and transmission electron microscope observed autophagosomes. Pull-down assay and dual luciferase reporter gene assay were used to verify the targeting relationship among TUG1, miR-29 and PTEN. The effects of TUG1 on biological behaviors of renal tubular cells were evaluated by simulating the acute renal injury induced by I/R in vitro.Results: In vivo, the levels of BUN, SCr and MDA in serum of I/R-treated rats were increased, SOD level and autophagosomes were reduced, tubule epithelial cells were necrotic, and TUG1 was upregulated in renal tissues of I/R-treated rats, which were reversed by TUG1 knockdown. Autophagy inhibition attenuated the protective effect of TUG1 knockdown on I/R-treated rats. TUG1 could competitively bind to miR-29 to promote PTEN expression. In vitro, low expression of TUG1 promoted proliferation and autophagy of renal tubular cells and inhibited apoptosis.Conclusion: TUG1 knockdown promotes autophagy and improves acute renal injury in I/R-treated rats by binding to miR-29 to silence PTEN.

scholarly journals Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes

2015 ◽  
Vol 59 (12) ◽  
pp. 7489-7496 ◽  
Author(s):  
Bo Yun ◽  
Mohammad A. K. Azad ◽  
Cameron J. Nowell ◽  
Roger L. Nation ◽  
Philip E. Thompson ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Rat Kidney ◽  
Antimicrobial Activities ◽  
Core Structure ◽  
Confocal Imaging ◽  
Limiting Factor ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Apoptotic Effects

ABSTRACTPolymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity.

scholarly journals 3D-confocal structural analysis of bone marrow-derived renal tubular cells during renal ischemia/reperfusion injury

2005 ◽  
Vol 86 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Hideyoshi Toyokawa ◽  
Atsunori Nakao ◽  
Donna B Stolz ◽  
Anna J Romanosky ◽  
Michael A Nalesnik ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Structural Analysis ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Ischemia Reperfusion Injury ◽  
Renal Tubular

scholarly journals Palmitate aggravates proteinuria-induced cell death and inflammation via CD36-inflammasome axis in the proximal tubular cells of obese mice

2018 ◽  
Vol 315 (6) ◽  
pp. F1720-F1731 ◽  
Author(s):  
Lung-Chih Li ◽  
Jenq-Lin Yang ◽  
Wen-Chin Lee ◽  
Jin-Bor Chen ◽  
Chien-Te Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Caspase 1 ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Nlrp3 Inflammasomes

High levels of serum free fatty acids (FFAs) and proteinuria have been implicated in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1β, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1β, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1β, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy.

MDM2 inhibition improves cisplatin-induced renal injury in mice via inactivation of Notch/hes1 signaling pathway

2020 ◽  
pp. 096032712095215
Author(s):  
X Luo ◽  
L Zhang ◽  
G-D Han ◽  
P Lu ◽  
Y Zhang
Keyword(s):  
Signaling Pathway ◽  
Renal Injury ◽  
Cell Apoptosis ◽  
Renal Tissue ◽  
Tunel Staining ◽  
Acute Renal Injury ◽  
Renal Tubular ◽  
Injury Models

Objective: To explore the potential function of MDM2-mediated Notch/hes1 signaling pathway in cisplatin-induced renal injury. Methods: The acute renal injury models of mice after intraperitoneal injection of cisplatin in vivo, and the apoptotic models of human renal tubular epithelial (HK-2) cells induced by cisplatin in vitro, were conducted respectively. The renal function-related parameters were measured. The renal tissue pathological changes and apoptosis were observed by PAS staining and TUNEL staining, respectively. Cell viability and apoptosis were detected by MTT and flow cytometry. Notch/hes1 pathway-related proteins were tested by Western blotting. Results: After mice injected by cisplatin, the levels of Cr, BUN, urine cystatin C, urine NGAL and urine ACR were increased and GFR was decreased with the elevation of renal tubular injury scores, the upregulation of the expressions of MDM2, N1ICD, Hes1 and Cleaved caspase-3, as well as the enhancement of cell apoptosis accompanying decreased ratio of Bcl-2/Bax. However, these cisplatin-induced renal injuries of mice have been improved by MDM2 inhibition. Besides, the declined viability, increased cytotoxicity, and enhanced apoptosis were observed in cisplatin-induced HK-2 cells, with the activated Notch/hes1 pathway. Notably, the phenomenon was alleviated in cisplatin-induced HK-2 cells transfected with MDM2 shRNA, but was severer in those co-treated with AdMDM2. Moreover, Notch1 siRNA can reverse the injury of AdMDM2 on HK-2 cells. Conclusion: Inhibiting MDM2 could reduce cell apoptosis through blocking Notch/hes1 signaling pathway, thus alleviating the acute renal injury caused by cisplatin.

scholarly journals Caspofungin is less nephrotoxic than amphotericin B in vitro and predominantly damages distal renal tubular cells

2005 ◽  
Vol 20 (10) ◽  
pp. 2071-2079 ◽  
Author(s):  
Binytha Wegner ◽  
Patrick Baer ◽  
Stefan Gauer ◽  
Gerhard Oremek ◽  
Ingeborg A. Hauser ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular
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