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ABSTRACT: Vascular endothelial cells play an important role in leukocyte trafficking during the inflammatory process. Proinflammatory cytokines activate the expression of cell adhesion molecules in endothelial cells. Janus kinase (JAK) and signal transducer and activator of transcription (STAT) are important intracellular cytokine signaling molecules that are involved in immune responses. The purpose of this study was to investigate the effect of JAK3 inhibition on the expression of tumor necrosis factor (TNF)-α-induced cell adhesion molecules in vascular endothelial cells and to evaluate the therapeutic potential of JAK3 for myocardial vascular permeability in endotoxemic mice. A JAK3 inhibitor, JANEX-1, decreased the TNF-α-induced expression of intercellular adhesion molecule (ICAM)-1, VCAM (vascular cell adhesion molecule)-1 and fractalkine in human umbilical vein endothelial cells (HUVECs). The downregulation of the expression of these cell adhesion molecules by JANEX-1 was mediated via suppression of STAT3 phosphorylation and nuclear factor-κB (NF-κB) activation. In endotoxemic mice, pretreatment with JANEX-1 prevented not only an increase in the cardiac ICAM-1 expression by LPS in the arteriolar and capillary endothelial cells, but also myocardial vascular leakage. These results suggest that inhibition of the JAK/STAT pathway by JANEX-1 ameliorates the expression of TNF-α-induced cell adhesion molecules in HUVECs and improves myocardial vascular permeability.
International Journal of Molecular Medicine 05/2012; 29(5):864-70. · 1.98 Impact Factor
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Yu Jin Jung,
Hyun Ju Choi,
Jung Eun Lee,
Ae Sin Lee,
Kyung Pyo Kang,
Sik Lee,
Sung Kwang Park,
Tae Sun Park,
Heung Yong Jin,
Sang Young Lee,
Duk Hoon Kim,
Won Kim
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ABSTRACT: Metabolic syndrome consists of metabolic abnormality with central obesity, hypertriglyceridemia, insulin resistance and hypertension. Adipose tissue has been known as a primary site of insulin resistance and its adipocyte size may be correlated with the degree of insulin resistance. A designed angiopoietin-1, COMP-Angiopoietin-1 (COMP-Ang1), mitigated high-fat diet-induced insulin resistance in skeletal muscle. In this study, we examined effects of COMP-Ang1 on adipocyte droplet size, vascular endothelial cell density in adipose tissue and metabolic parameters in db/db mice by administering COMP-Ang1 or LacZ (as a control) adenovirus. Administration of COMP-Ang1 decreased fat droplet diameter in epididymal and abdominal visceral adipocyte and visceral fat content in db/db mice. The density of vascular endothelial cell in adipose tissue was increased in db/db mice after treatment with COMP-Ang1. Serum resistin and tumor necrosis factor-α level was lower after treatment with COMP-Ang1 in db/db mice. COMP-Ang1 caused a restoration of fasting glycemic control in db/db mice and decreased serum insulin level and insulin resistance measured by HOMA index. These findings indicate that COMP-Ang1 regulates adipocyte fat droplet diameter, vascular endothelial cell density and metabolic parameters in db/db mice.
Biochemical and Biophysical Research Communications 03/2012; 420(3):498-504. · 2.48 Impact Factor
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ABSTRACT: Fucoxanthin, one of the main marine carotenoids, is abundant in macro- and microalgae. Here, fucoxanthin was isolated and structurally identified as the major carotenoid in the diatom Phaeodactylum tricornutum through chromatographic and spectroscopic methods, such as liquid chromatography-positive-ion atmospheric pressure chemical ionization/mass spectroscopy and nuclear magnetic resonance. This pigment was quantified by reverse-phase high-performance liquid chromatography, and a number of extraction procedures were assessed to investigate the effect of solvent type, extraction time, temperature, and extraction method (maceration, ultrasound-assisted extraction, Soxhlet extraction, and pressurized liquid extraction). Among the investigated solvents, ethanol provided the best fucoxanthin extraction yield (15.71 mg/g freeze-dried sample weight). Fucoxanthin content in the extracts produced by the different methods was quite constant (15.42-16.51 mg/g freeze-dried sample weight) but increased steeply based on the percentage of ethanol in water, emphasizing the importance of ethanol in the extraction. The results indicate that P. tricornutum is a rich source of fucoxanthin (at least ten times more abundant than that in macroalgae) that is easily extracted with ethanol, suggesting potential applications in human and animal food, health, and cosmetics.
Applied biochemistry and biotechnology 02/2012; 166(7):1843-55. · 1.94 Impact Factor
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ABSTRACT: As the increased acetylation of p65 is linked to nuclear factor-κB (NF-κB) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-κB and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-κB and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-κB p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-κB during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-κB p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-κB through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.
Biochemical and Biophysical Research Communications 02/2012; 419(2):206-10. · 2.48 Impact Factor
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ABSTRACT: The human cathelicidin antimicrobial protein hCAP18, which includes the C-terminal peptide LL-37, is a multifunctional protein. As a possible approach to enhancing the resistance to plant disease, a DNA fragment coding for hCAP18/LL-37 was fused at the C-terminal end of the leader sequence of endopolygalacturonase-inhibiting protein under the control of the cauliflower mosaic virus 35S promoter region. The construct was then introduced into Brassica rapa. LL-37 expression was confirmed in transgenic plants by reverse transcription-polymerase chain reaction and western blot analysis. Transgenic plants exhibited varying levels of resistance to bacterial and fungal pathogens. The average size of disease lesions in the transgenic plants was reduced to less than half of that in wild-type plants. Our results suggest that the antimicrobial LL-37 peptide is involved in wide-spectrum resistance to bacterial and fungal pathogen infection.
Plant Biotechnology Reports 01/2012; 6(1):39-46. · 1.19 Impact Factor
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Duk Hoon Kim, Yu Jin Jung,
Jung Eun Lee,
Ae Sin Lee,
Kyung Pyo Kang,
Sik Lee,
Sung Kwang Park,
Myung Kwan Han,
Sang Yong Lee,
Kunga Mohan Ramkumar,
Mi Jeong Sung,
Won Kim
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ABSTRACT: Nephrotoxicity is one of the important dose-limiting factors during cisplatin treatment. There is a growing body of evidence that activation of p53 has a critical role in cisplatin-induced renal apoptotic injury. The nicotinamide adenine dinucleotide-dependent protein deacetylase SIRT1 decreases apoptosis through deacetylating of p53, and resveratrol is known as an activator of SIRT1. To study the role of SIRT1 in cisplatin-induced renal injury through interaction with p53, mouse proximal tubular cells (MPT) were treated with cisplatin and examined the expression level of SIRT1, acetylation of p53, PUMA-α, Bax, the cytosolic/mitochondrial cytochrome c ratio, and active caspase-3. The expression of SIRT1 was decreased by cisplatin. Resveratrol, a SIRT1 activator, ameliorated cisplatin-induced acetylation of p53, apoptosis, and cytotoxicity in MPT cells. In addition, resveratrol remarkably blocked cisplatin-induced decrease of Bcl-xL in MPT cells. Further specific SIRT1 inhibition with EX 527 or small interference RNA specific to SIRT1 reversed the effect of resveratrol on cisplatin-induced toxicity. Inhibition of p53 by pifithrin-α reversed the effect of EX527 in protein expression of PUMA-α, Bcl-xL, and caspase-3 and cytotoxicity in MPT cells. SIRT1 protein expression after cisplatin treatment was significantly decreased in the kidney. SIRT1 activation by resveratrol decreased cisplatin-induced apoptosis while improving the glomerular filtration rate. Taken together, our findings suggest that the modulation of p53 by SIRT1 could be a possible target to attenuate cisplatin-induced kidney injury.
AJP Renal Physiology 05/2011; 301(2):F427-35. · 4.42 Impact Factor
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Ae Sin Lee,
Duk Hoon Kim,
Jung Eun Lee, Yu Jin Jung,
Kyung Pyo Kang,
Sik Lee,
Sung Kwang Park,
Jae Yong Kwak,
Sang Yong Lee,
Suk Tae Lim,
Mi Jung Sung,
Suk Ran Yoon,
Won Kim
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ABSTRACT: Cancer therapy often produces anemia, which is treated with erthropoietin (EPO) to stimulate erythrocyte production. However, concerns have recently arisen that EPO treatment may promote later tumor metastasis and mortality. The mechanisms underlying such effects are unknown, but it is clear that EPO has pleiotropic effects in cell types other than hematopoietic cells. In this study, we investigated how EPO affects lymphangiogenesis and lymph node tumor metastasis in mouse models of breast cancer and melanoma. In these models, EPO increased lymph node lymphangiogenesis and lymph node tumor metastasis in a manner associated with increased migration, capillary-like tube formation, and dose- and time-dependent proliferation of human lymphatic endothelial cells. EPO increased sprouting of these cells in a thoracic duct lymphatic ring assay. These effects were abrogated by cotreatment with specific inhibitors of phosphoinositide 3-kinase or mitogen-activated protein kinase, under conditions in which EPO increased Akt and extracellular signal-regulated kinase 1/2 phosphorylation. Intraperitoneal administration of EPO stimulated peritoneal lymphangiogenesis, and systemic treatment of EPO increased infiltration of CD11b(+) macrophages in tumor-draining lymph nodes. Finally, EPO increased VEGF-C expression in lymph node-derived CD11b(+) macrophages as well as in bone marrow-derived macrophages in a dose- and time-dependent manner. Our results establish that EPO exerts a powerful lymphangiogenic function and can drive both lymph node lymphangiogenesis and nodal metastasis in tumor-bearing animals.
Cancer Research 05/2011; 71(13):4506-17. · 7.86 Impact Factor
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Kyung Pyo Kang,
Sung Kwang Park,
Duk Hoon Kim,
Mi Jeong Sung, Yu Jin Jung,
Ae Sin Lee,
Jung Eun Lee,
Kunka Mohanram Ramkumar,
Sik Lee,
Moon Hyang Park,
Si-Gyun Roh,
Won Kim
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ABSTRACT: Cisplatin chemotherapy often causes acute kidney injury in cancer patients. The causative mechanisms of cisplatin-induced acute kidney injury include renal inflammation, activation of p53 tumour suppressor protein and tubular apoptosis. Luteolin, a flavone found in medicinal herbs and plants, has been reported to exhibit anti-inflammatory, antioxidant and anticarcinogenic activities. The purpose of this study was to investigate the anti-apoptotic effect of luteolin on cisplatin-induced acute kidney injury and the molecular mechanism.
C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without treatment with luteolin (50 mg/kg for 3 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of luteolin on cisplatin-induced expression of renal p53, PUMA-α and Bcl-2 family proteins were evaluated.
Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. Treatment of cisplatin-treated mice with luteolin significantly improved renal dysfunction, reducing tubular cell damage, oxidative stress and apoptosis. Examination of molecules involving apoptosis of the kidney revealed that treatment of cisplatin increased the levels of p53 and its phosphorylation, PUMA-α, Bax and caspase-3 activity that were significantly decreased by treatment with luteolin.
These results indicate that cisplatin induces acute kidney injury by regulation of p53-dependent renal tubular apoptosis and that luteolin ameliorates the cisplatin-mediated nephrotoxicity through down-regulation of p53-dependent apoptotic pathway in the kidney.
Nephrology Dialysis Transplantation 03/2011; 26(3):814-22. · 3.40 Impact Factor
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ABSTRACT: Genistein is a polyphenolic nonsteroidal isoflavonoid with estrogen-like activity has been shown to have anticancer, antioxidant, and anti-inflammatory activities. Fractalkine is a unique chemokine that functions as a chemoattractant and an adhesion molecule on endothelial cells activated by proinflammatory cytokines. In this study, we investigated the effects of genistein (5-25 muM) on fractalkine expression in human umbilical vein endothelial cells (HUVECs) and on its receptor, CX3CR1, in THP-1 cells in response to treatment with tumor necrosis factor (TNF)- alpha. TNF-alpha significantly induced fractalkine expression in endothelial cells. Genistein decreased TNF-alpha-induced fractalkine expression through suppression of Akt and p38 phosphorylation and NF-kappaB activities. Genistein also strongly suppressed TNF-alpha-induced expression of CX3CR1 in monocytes. Genistein suppressed TNF-alpha-stimulated adhesion of monocytes to HUVECs. Immunohistochemical analysis revealed that genistein suppressed the in vivo lipopolysaccharide (LPS)-induced arterial endothelial fractalkine expression in the heart, kidney, and small intestine. These results suggest that genistein may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury under vascular inflammatory conditions.
Cellular Physiology and Biochemistry 01/2010; 26(3):431-40. · 2.86 Impact Factor
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Duk Hoon Kim, Yu Jin Jung,
Ae Sin Lee,
Sik Lee,
Kyung Pyo Kang,
Tae Hwan Lee,
Sang Yong Lee,
Kyu Yun Jang,
Woo Sung Moon,
Kyu-Sil Choi,
Kwon-Ha Yoon,
Mi Jeong Sung,
Sung Kwang Park,
Won Kim
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ABSTRACT: During sepsis endothelial dysfunction is an important pathogenetic mechanism in acute kidney injury (AKI). Lipopolysaccharide (LPS)-induced endotoxemia is associated with renal hemodynamic changes such as alterations of renal blood flow (RBF), vascular resistance, and glomerular filtration rate. We used adenoviral delivery of an engineered variant of native angiopoietin-1 (COMP-angiopoietin-1) containing anti-inflammatory and anti-permeability functions, to determine if regulation of renal endothelial cell dysfunction may have a beneficial role in preventing AKI during LPS-induced endotoxemia in mice. This treatment prevented the endotoxin-induced decrease of RBF and mean arterial pressure while improving glomerular filtration rate. Treatment also mitigated the effects of LPS on renal intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 protein expression, the number of ER-HR3-positive macrophages that infiltrated the kidney, serum nitrate/nitrite levels, renal inducible nitric oxide synthase protein expression, the induction of tubular epithelial reactive oxygen and nitrogen species, and renal microvascular permeability. Our findings show that COMP-angiopoietin-1, an endothelium-oriented therapeutic agent, protects against AKI caused by endotoxemia.
Kidney International 10/2009; 76(11):1180-91. · 6.61 Impact Factor
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ABSTRACT: Ischemia followed by reperfusion induces microvascular endothelial cell injury, leading to the loss of functions such as regulation of vascular tone, tissue perfusion, permeability, and inflammation in kidney. Improvement of this endothelial dysfunction could be a good approach to treating ischemia-reperfusion-induced renal injury. Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is a variant of native angiogenic factor angiopoietin-1 engineered to have higher activity. We evaluated the protective effect of COMP-Ang1 in an ischemia-reperfusion renal injury model. COMP-Ang1 preserved renal peritubular capillaries after ischemia-reperfusion injury without recruiting pericytes. Pretreatment with COMP-Ang1 attenuated the increase of blood urea nitrogen and serum creatinine levels after ischemia-reperfusion. In addition, the morphological examination indicated less tubular injury in mice pretreated with COMP-Ang1 than in those treated with the vehicle. COMP-Ang1 treatment reduced the increase in the number of Gr-1-positive neutrophils or ER-HR3-positive macrophages infiltrating kidneys, increased phosphorylation of Akt, and preserved renal tissue perfusion flow and microvascular permeability. Furthermore, COMP-Ang1 decreased renal interstitial fibrosis 30 days after the ischemia-reperfusion injury. In conclusion, COMP-Ang1 can be a possible endothelial cell-targeted therapy for preventing ischemia-reperfusion-induced acute kidney injury.
AJP Renal Physiology 09/2009; 297(4):F952-60. · 4.42 Impact Factor
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ABSTRACT: Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (alpha-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-kappaB (NF-kappaB) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of alpha-LA during cisplatin-induced renal injury and to examine the mechanisms of protection.
C57BL/6 mice were given cisplatin (20 mg/kg) with or without alpha-LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of alpha-LA on NF-kappaB activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappaB p65 subunits in kidney tissue.
Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by alpha-LA treatment. alpha-LA decreased the tissue levels of tumour necrosis factor-alpha, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. alpha-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- kappaB p65 subunits in kidney tissue.
These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappaB activity.
Nephrology Dialysis Transplantation 06/2009; 24(10):3012-20. · 3.40 Impact Factor
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Duk Hoon Kim,
Sang-Ok Moon, Yu Jin Jung,
Ae Sin Lee,
Kyung Pyo Kang,
Tae Hwan Lee,
Sik Lee,
Ok Hee Chai,
Chang Ho Song,
Kyu Yun Jang,
Mi Jeong Sung,
Xin Zhang,
Sung Kwang Park,
Won Kim
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ABSTRACT: Mast cells regulate both inflammatory responses and tissue repair in human diseases but there are conflicting reports on the role of these cells in the pathogenesis of various kidney diseases. Here we measured mast cell function in unilateral ureteral obstruction, a well-characterized model of renal fibrosis, using Kit(W)/Kit(W-v) mice genetically deficient in mast cells, wild-type mice, and deficient mice reconstituted by adoptive transfer with mast cells from the wild-type animals. Mast cell-deficient mice had higher levels of renal tubular damage, more stromal fibrosis, higher numbers of infiltrating ERHR3-positive macrophages and CD3-positive T cells, and higher tissue levels of profibrotic transforming growth factor-beta1 than wild-type mice or mice reconstituted by adoptive transfer of mast cells 3 weeks after ureteral obstruction. Similarly, while wild-type and adoptively transferred mice had increased alpha-smooth muscle actin and decreased E-cadherin expression, which are indicators of epithelial-mesenchymal transition, the obstructed kidneys of the mast cell-deficient mice had significant attenuation of those indicators. Thus, our study suggests that mast cells protect the kidney against fibrosis by modulation of inflammatory cell infiltration and by transforming growth factor-beta1-driven epithelial-to-mesenchymal transitions.
Kidney International 03/2009; 75(10):1031-8. · 6.61 Impact Factor
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Ae Sin Lee, Yu Jin Jung,
Duk Hoon Kim,
Tae Hwan Lee,
Kyung Pyo Kang,
Sik Lee,
Nae Ho Lee,
Mi Jeong Sung,
Dae Young Kwon,
Sung Kwang Park,
Won Kim
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ABSTRACT: Epigallocatechin-3-O-gallate (EGCG), the main catechin in green tea, has anti-oxidant, anti-atherosclerotic and anti-inflammatory properties. Fractalkine, a chemokine involved in inflammation and early atherosclerotic processes, acts as a chemoattractant as well as an adhesion molecule in endothelial cells activated by proinflammatory cytokines. In the present study, we investigated the effect of EGCG on fractalkine expression in TNF-alpha-induced human umbilical vein endothelial cells (HUVECs). EGCG decreased TNF-alpha-induced fractalkine mRNA and protein expression in HUVECs in a time-dependent manner. EGCG suppressed the TNF-alpha-induced phosphorylation and degradation of IkappaB-alpha, thereby decreasing the phosphorylation and nuclear translocation of the NF-kappaB p65 subunit in HUVECs. The DNA binding activity of the NF-kappaB p65 subunit was lower in EGCG-pretreated HUVECs than in those treated with TNF-alpha alone. Furthermore, EGCG inhibited monocyte adhesion to HUVECs stimulated by TNF-alpha. The silencing of fractalkine with an siRNA or treatment with a blocking antibody against fractalkine suppressed the TNF-alpha-induced increase in monocyte adhesion. These results demonstrate that EGCG prevents TNF-alpha-induced vascular endothelial fractalkine expression.
Cellular Physiology and Biochemistry 01/2009; 24(5-6):503-10. · 2.86 Impact Factor
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Mi Jeong Sung,
Duk Hoon Kim, Yu Jin Jung,
Kyung Pyo Kang,
Ae Sin Lee,
Sik Lee,
Won Kim,
Munkhtugs Davaatseren,
Jin-Taek Hwang,
Hyun-Jin Kim,
Myung Sunny Kim,
Dae Young Kwon,
Sung Kwang Park
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ABSTRACT: Oxidative stress and inflammation contribute to the pathogenesis of cisplatin-induced nephrotoxicity. We found that genistein, a tyrosine kinase inhibitor with broad specificities, and which also has estrogen-like activity, had protective effects on cisplatin-induced renal injury in mice. Genistein significantly decreased reactive oxygen species production, the expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 proteins, as well as the translocation of the p65 subunit of nuclear factor-kappaB into the nucleus and the infiltration of macrophages, all of which were increased in the kidney by cisplatin treatment. Genistein also decreased cisplatin-induced apoptosis by regulating p53 induction in kidney. Genistein significantly reduced reactive oxygen species production in cisplatin-treated normal human kidney HK-2 cells. These studies show that genistein or similar compounds might be useful in prevention of cisplatin-induced renal injury.
Kidney International 09/2008; 74(12):1538-47. · 6.61 Impact Factor
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Sik Lee,
Won Kim,
Duk Hoon Kim,
Sang-Ok Moon, Yu Jin Jung,
Ae Sin Lee,
Kyung Pyo Kang,
Kyu Yun Jang,
Sang Yong Lee,
Mi Jeong Sung,
Gou Young Koh,
Sung Kwang Park
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ABSTRACT: Peritubular capillary injury induces chronic hypoxia in the renal tubulointerstitium, and renal peritubular capillary dysfunction is an early event that contributes to tubulointerstitial fibrosis. Cyclosporine A (CsA) is a potent immunosuppressant and improves survival of renal allografts. However, the limitation of CsA use is chronic nephrotoxicity. A soluble, stable and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1 has been developed. We investigated whether COMP-Ang1 ameliorates CsA-induced renal injury.
CsA-treated mice were injected with recombinant adenovirus expressing either COMP-Ang1 or LacZ. Histology, inflammatory, haemodynamic and fibrotic parameters, and signalling pathway were evaluated.
Histologic examination showed that COMP-Ang1 significantly decreased CsA-induced tubular damage and tubulointerstitial fibrosis. CsA-induced increases in macrophage infiltration and expression of MCP-1 and ICAM-1 after CsA treatment were significantly reduced by COMP-Ang1. Treatment with COMP-Ang1 also decreased the CsA-induced increases in TGF-beta1 and Smad 2/3 levels while increasing Smad 7 levels. Laser-Doppler sonographic findings and endothelial factor VIII staining revealed that COMP-Ang1 preserved the integrity of peritubular vasculature and intrarenal haemodynamics from the CsA-induced renal injury. COMP-Ang1 inhibited tubular cell apoptosis while increasing tubular cell proliferation in CsA-induced renal injury.
These results indicate that COMP-Ang1 exhibited a protective effect on damaged peritubular capillaries, haemodynamic alteration and inflammation in CsA-induced renal injury. Thus, COMP-Ang1 may be useful as a therapeutic and prophylactic agent for specific protection against endothelial dysfunction and inflammation.
Nephrology Dialysis Transplantation 06/2008; 23(9):2784-94. · 3.40 Impact Factor
