• Childhood Kidney Diseases
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• v.19 no.2
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• pp.89-97
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• 2015

Background: We conducted this experimental study to examine whether human adipose-derived stem cells (ADSCs) are effective in achieving a recovery of damaged renal tubular epithelial cells in an animal model of cisplatin-induced acute kidney injury using rats. Methods: To examine the in vitro effects of ADSCs in improving nephrotoxicity, we treated mouse renal tubular epithelial cells with both ADSCs and cisplatin mouse renal tubular epithelial cells. And we equally divided 30 male white Sprague-Dawley (SD) rats into the three groups: the control group (intraperitoneal injection of a sterile saline), the cisplatin group (intraperitoneal injection of cisplatin) and the ADSC group (intraperitoneal injection of cisplatin and the hADSC via the caudal vein). At five days after the treatment with cisplatin, serum levels of blood urine nitrogen (BUN) and creatinine were measured from each SD rat. We performed histopathologic examinations of tissue samples obtained from the kidney. Results: The degree of the expression of TNF-${\alpha}$ and that of Bcl-2 were significantly higher and lower respectively, in cisplatin group (P<0.05). Serum levels of BUN (P=0.027) and creatinine (P=0.02) were significantly higher in cisplatin group. On histopathologic examinations, there was a significant difference in the ratio of the renal injury between cisplatin group and ADSC group (P=0.002). Conclusion: The ADSCs might have a beneficial effect in regenerating the damaged renal tubular epithelial cells.

• Biomedical Science Letters
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• v.9 no.4
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• pp.189-193
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• 2003

This study was undertaken to investigate the effect of baicalein, a major flavone component of Scutellaria balicalensis Georgi, on oxidant-induced cell injury in renal epithelial cells. Opossum kidney cells, an established proximal tubular epithelial cells, were used as a cell model of renal epithelial cells and t-butylhydroperoxide (tBHP) as an oxidant drug model. Cell viability was measured by MTT assay and lipid peroxidation was estimated by measuring the content of malondialdehyde, a product of lipid peroxidation. Exposure of cells to tBHP caused cell death and its effect was dose-dependent over concentration range of 0.1~1.0 mM. When cells were exposed to tBHP in the presence of various concentrations (0.1~10 $\mu$M) of baicalein, tBHP-induced cell death was prevented with a manner dependent of baicalein concentration. tBHP induced A TP depletion, which was significantly prevented by baicalein. Similarly, tBHP-induced DNA damage was prevented by baicalein. tBHP produced a marked increase in lipid peroxidation and its effect was completely inhibited by baicalein. These results indue ate that tBHP induces cell injury through a lipid peroxidation-dependent mechanism in renal epithelial cells, and baicalein prevented oxidant-induced cell injury via antioxidant action inhibiting lipid peroxidation. In addition, these results suggest that baicalein may be a candidate for development of drugs which are effective in preventing and treating renal diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.533-540
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• 2023

Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.1-7
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• 2006

Osteopontin (OPN) is a glycosylated phosphoprotein which mediates cell adhesion and migration, and is produced by bone, macrophages, endothelial cells, and epithelial cells. The many regulatory functions of OPN include bone remodeling, tumor invasion, wound repair, and promotion of cell survival. It is produced by renal tubular epithelial cells, and expression is upregulated in glomerulonephritis, hypertension, ischemic acute renal failure, renal ablation, and UUO. In this review, we discuss about osteopontin in general aspect, expression, role on the development and pathologic condition of neonatal kidney.

• Korean Journal of Clinical Laboratory Science
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• v.42 no.1
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• pp.46-54
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• 2010

Ceramide induces cell death in a variety of cell types however, the underlying molecular mechanisms related to renal epithelial cells remain unclear. The present study was undertaken to determine the role of extracellular signal-regulated protein kinase (ERK) in ceramide-induced cell death in renal epithelial cells. An established renal proximal tubular cell line of opossum kidney (OK) cells was used for this research. Ceramide induced apoptotic cell death in these cells. Western blot analysis showed that ceramide induced activation of ERK. The ERK activation and cell death induced by ceramide were prevented by the ERK inhibitor PD98059. Ceramide caused cytochrome C release from mitochondria into the cytosol as well as activation of caspase-3. Both effects were prevented by PD98059. The ceramide-induced cell death was also prevented by a caspase inhibitor. These results suggest that ceramide induces cell death through an ERK-dependent mitochondrial apoptotic pathway in OK cells.

• Journal of Acupuncture Research
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• v.19 no.4
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• pp.190-199
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• 2002

Objective : This study was performed to determine if Scutellaria balicalensis Georgi extract (SbGE) prevents oxidant-induced membrane transport dysfunction in renal tubular cells. Methods : Membrane transport function was estimated by measuring $Na^+$-dependent inorganic phosphate transport in opossum kidney (OK) cells. $H_2O_2$ inhibited phosphate transport in a dose-dependent manner. Results : The inhibitory effect of $H_2O_2$ was significantly prevented SbGE over concentration range of 0.005-0.05%. $H_2O_2$ caused ATP depletion, which was prevented by SbGE. $H_2O_2$ induced the loss of mitochondrial function as evidenced by decreased MTT reduction and its effect was prevented by SbGE. The $H_2O_2$-induced inhibition of phosphate transport was not affected by a potent antioxidant DPPD, but the inhibition was prevented by an iron chelator deferoxamine, suggesting that $H_2O_2$ inhibits $Na^+$-dependent phosphate transport via an iron-dependent nonperoxidative mechanism in renal tubular cells. Conclusion : These data suggest that SbGE may exert the protective effect against oxidant-induced membrane transport dysfunction by a mechanism similar to iron chelators in renal epithelial cells. However, furher studies should be carried out to find the active ingredient(s) of SbGE that exerts the protective effect.

• BMB Reports
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• v.56 no.3
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• pp.196-201
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• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• The Korean Journal of Cytopathology
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• v.5 no.1
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• pp.65-70
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• 1994

We describe a case of fine needle aspiration cytology of renal angiomyolipoma which was not associated with the clinical complex of tuberous sclerosis and was incidentally found. It was a solitary lesion and the clinical impression before needle aspiration was renal ceil carcinoma. The aspirated specimen showed mature fat cells, clusters of renal tubular epithelial cells and sheets of pleomorphic smooth muscle cells with fibrillary cytoplasm. The nuclei of smooth muscle celis varied in size and shape. Since the treatment of renal angiomyolipoma differs from that of renal ceil carcinoma, the preoperative cytological diagnosis is of great value.

• The Korean journal of internal medicine
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• v.34 no.1
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• pp.146-155
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• 2019

Background/Aims: Indoxyl sulfate (IS) is a uremic toxin and an important causative factor in the progression of chronic kidney disease. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was shown to exhibit protective effects in kidney injury. Here, we investigated the effects of paricalcitol treatment on IS-induced renal tubular injury. Methods: The fluorescent dye 2',7'-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following IS administration in human renal proximal tubular epithelial (HK-2) cells. The effects of IS on cell viability were determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and levels of apoptosis-related proteins (Bcl-2-associated protein X [Bax] and B-cell lymphoma 2 [Bcl-2]), nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65, and phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) were determined by semiquantitative immunoblotting. The promoter activity of $NF-{\kappa}B$ was measured by luciferase assays and apoptosis was determined by f low cytometry of cells stained with f luorescein isothiocyanate-conjugated Annexin V protein. Results: IS treatment increased ROS production, decreased cell viability and induced apoptosis in HK-2 cells. IS treatment increased the expression of apoptosis-related protein Bax, decreased Bcl-2 expression, and activated phosphorylation of MAPK, $NF-{\kappa}B$ p65, and Akt. In contrast, paricalcitol treatment decreased Bax expression, increased Bcl-2 expression, and inhibited phosphorylation of MAPK, $NF-{\kappa}B$ p65, and Akt in HK-2 cells. $NF-{\kappa}B$ promoter activity was increased following IS, administration and was counteracted by pretreatment with paricalcitol. Additionally, flow cytometry analysis revealed that IS-induced apoptosis was attenuated by paricalcitol treatment, which resulted in decreased numbers of fluorescein isothiocyanate-conjugated Annexin V positive cells. Conclusions: Treatment with paricalcitol inhibited IS-induced apoptosis by regulating MAPK, $NF-{\kappa}B$, and Akt signaling pathway in HK-2 cells.

• Preventive Nutrition and Food Science
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• v.17 no.2
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• pp.101-108
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• 2012

Interruption or prolonged reduction and subsequent restoration of blood flow into the kidney triggers the generation of a burst of reactive oxygen species (ROS), leading to injury in the tubular epithelial cells. In this study, we determined whether methanol extract of goat's-beard (Aruncus dioicus) (extract) could prevent this ischemia/reperfusion injury. When in vitro radical scavenging activity of the extract was measured using a DPPH radical quenching assay, the extract displayed slightly lower activity than ascorbic acid. One hour after administration of the extract (400 mg/kg) by intraperitoneal injection in rats, renal ischemia/reperfusion injury was generated by clamping the left renal artery for forty minutes, followed by 24 hr restoration of blood circulation. Prior to clamping the left renal artery, the right renal artery was removed. Compared with the vehicle-treated group, pretreatment with the extract significantly reduced the tubular epithelial cell injury by 37% in the outer medulla region, and consequently reduced serum creatinine concentration by 39%. Reduction in the cell injury was mediated by attenuation of Bax/Bcl-2 ratio, inhibition of caspase-3 activation from procaspase-3, and subsequent reduction in the number of apoptotic cells. Thus, goat's-beard (Aruncus dioicus) might be developed as a prophylactic agent to prevent acute kidney injury.