• The Korean Journal of Physiology
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• 제16권2호
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• pp.165-175
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• 1982

Changes in handling of $Li^+$ by contralateral kidney during acute $Li^+$ loading were investigated immediately after unilateral ureteral obstruction. Carotid artery, jugular vein, renal vein and ureter of experimental animal were catheterized and renal venous flow was shunted to .external jugular vein. In experimental group right ureter was ligated. One to two hours after operation a single shot of LiCl solution (2 mEq/kg) was intravenously injected and then .arterial, renal venous blood and urine samples were taken sequentially for 1 to $1{\frac{1}{2}}$ hours. Urine volume, plasma and urinary concentrations of $Li^+$, $Na^+$ and $K^+$ were measured and urinary excretion of them were calculated. Results obtained were as follows: 1) In experimental group urine volume, urinary excretion of $Na^+$, and $K^+$ by contralateral kidney after unilateral ureteral obstruction were slightly larger than mean value of both kidney in control group. 2) During acute $Li^+$ loading contralateral kidney in experimental group showed limited $K^+$ excretion, but urinary flow and $Na^+$ excretion were comparable to mean value of both kidney in control group. 3) Urinary osmolar concentration in experimental group was much lower than that in control group, and it was maintained at low level even after Li loading. 4) In experimental group plasma$Li^+$ concentration decreased more slowly than in control group after a single shot of LiCl solution. 5) Urinary excretion of $Li^+$ in experimental group was markedly decreased, even lesseer than mean of both kidney in control group. 6) From the above results it was concluded that immediately after unilateral ureteral obstruction contralateral kidney showed normal water and $Na^+$ diuretic response to Li load but urinay $Li^+$ excretion was decreased and reclaimed $Li^+$ to systemic circulation.

• BMB Reports
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• 제53권11호
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• pp.594-599
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• 2020

Lin28a has diverse functions including regulation of cancer, reprogramming and regeneration, but whether it promotes injury or is a protective reaction to renal injury is unknown. We studied how Lin28a acts in unilateral ureteral obstruction (UUO)-induced renal fibrosis following unilateral ureteral obstruction, in a mouse model. We further defined the role of Lin28a in transforming growth factor (TGF)-signaling pathways in renal fibrosis through in vitro study using human tubular epithelium-like HK-2 cells. In the mouse unilateral ureteral obstruction model, obstruction markedly decreased the expression of Lin28a, increased the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin. In TGF-β-stimulated HK-2 cells, the expression of Lin28a was reduced and the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin was increased. Adenovirus-mediated overexpression of Lin28a inhibited the expression of TGF-β-stimulated type I collagen, α-SMA, vimentin and fibronectin. Lin28a inhibited TGF-β-stimulated SMAD3 activity, via inhibition of SMAD3 phosphorylation, but not the MAPK pathway ERK, JNK or p38. Lin28a attenuates renal fibrosis in obstructive nephropathy, making its mechanism a possible therapeutic target for chronic kidney disease.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.139-146
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• 2021

Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilateral ureteral obstruction (UUO)-induced kidney inflammation using IDH2 gene deleted mice (IDH2-/-). Eight- to 10-week-old female IDH2-/- mice and wild type (IDH2+/+) littermates were subjected to UUO and kidneys were harvested 5 days after UUO. IDH2 was not detected in the kidneys of IDH2-/- mice, while UUO decreased IDH2 in IDH2+/+ mice. UUO increased the expressions of markers of oxidative stress in both IDH2+/+ and IDH2-/- mice, and these changes were greater in IDH2-/- mice compared to IDH2+/+ mice. Bone marrow-derived macrophages of IDH2-/- mice showed a more migrating phenotype with greater ruffle formation and Rac1 distribution than that of IDH2+/+ mice. Correspondently, UUO-induced infiltration of monocytes/macrophages was greater in IDH2-/- mice compared to IDH2+/+ mice. Taken together, these data demonstrate that IDH2 plays a protective role against UUO-induced inflammation through inhibition of oxidative stress and macrophage infiltration.

• 대한한의학회지
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• 제39권2호
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• pp.1-12
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• 2018

Objectives: The objective of this study is to develop a new animal model with Kidney-hypofunction for Sasang Constitutional Medicine, especially for partial Soyangin(one of four constitution which has good digestive function and poor renal function) by Unilateral Ureteral Obstruction, and to estimate the factor related to obesity, dyslipidemia, and metabolic syndrome. Methods: The C57BL/6J mice were divided into 3 groups : normal group, high fat diet(HFD) control group, and HFD group with Unilateral Ureteral Obstruction(UUO). Then, the HFD control group and the experimental group were fed with high fat diet for 6 weeks. Food intake and body weight were measured at regular time by week. After the final experiment, blood was gathered for bloodchemical examination and organs(liver, fatty tissue) were remoed, weighted, and mRNA was analyzed with real-time PCR. Results: The weight growth rate with High fat diet went down by 8.35% in experimental group and had similar FER with the normal group, while HFD control group had higher weight growth rate and FER than any other groups. Also The experimental group had lower triglyceride and LDL cholesterol rate and higher glucose rate in serum. and in mRNA expression, GLUT-9, the protein related to excretion of uric acid and metabolic syndrome, expressed lower rate than that of HFD control group. and IL-6, a kind of cytokine related to obesity and metabolic syndrome, expressed more than HFD control group. Conclusions: It was found that Kidney-hypofunction animal-experimental model is susceptible to metabolic syndrome.

• 대한한의학방제학회지
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• 제31권3호
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• pp.133-144
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• 2023

Ureteral obstruction can be causes of renal dysfunction and renal injury at late period of kidney pathology. The purpose of this study was to determine the protective effects of Oryeongsan (ORS), Geumgwe-sinkihwan (GSH), and Jwagwieum (JGE) in rats with unilateral ureteral obstruction (UUO). The animal models were divided into five groups randomly at the age of 5 weeks; Control group: SD male rats (n=10), UUO group: SD male rats with UUO surgery (n=10), ORS group: SD male rats with UUO surgery + ORS 200 mg/kg/day (n=10), GSH group: SD male rats with UUO surgery + GSH 200 mg/kg/day (n=10), JGE group: SD male rats with UUO surgery + JGE 200 mg/kg/day (n=10). Treatment with ORS, GSH, and JGE significantly ameliorate creatinine clearance(Ccr). The present results also showed that ORS, GSH, and JGE improved the morphological aspects of renal tissues. These prescriptions also reduced the expression levels of cytokines such as TNF-α, IL-1β, and IL-6. In Kidney, UUO increased the expression levels of inflamasome markers such as NLRP3, ASC, and Caspase-1. However, ORS, GSH, and JGE suppressed these levele. Treatment with these prescriptions reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule -1 (KIM-1). Therefore, these findings suggest that ORS, GSH, and JGE has a protective effect on renal injury by alleviating renal inflammation and improving renal function in rats with UUO.

• 한국수정란이식학회지
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• 제30권3호
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• pp.261-263
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• 2015

A 10-year-old spayed female Yorkshire Terrier visited for a physical checkup. The bitch had a history of ovariohysterectomy for treatment of pyometra a year ago. On physical examination, the dog was bright and alert. Complete blood counts, serum biochemistry and blood gas analysis results did not show any deviations within normal ranges. Radiographic and ultrasonographic examinations revealed unilateral hydronephrosis and hydroureter of the right kidney and ureter, and obstruction of the distal ureter was observed. On the basis of these results, nephroureterectomy was performed. During the operation, the adhesion of the distal ureter and surrounding tissue cells were observed without the evidence of the ureteral ligation. The distal ureteral obstruction was presumed to be adhesion caused by fibrous tissue formation between ureter and retained broad ligament, or incompletely removed blood clots following ovariohysterectomy. This case report describes the occurrence of hydroureteronephrosis caused by adhesion of the distal ureter following ovariohysterectomy in a bitch.

• 대한수의학회지
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• 제39권1호
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• pp.230-239
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• 1999

Digital color doppler ultrasonographic system(DCDUS) has a lot of diagnostic functions. One of these is a detection of low velocity vessels in the organs of abdominal cavity. The purpose of study was to determine the clinical usefulness of DCDUS. Interlobar artery resistive index(RI), pulsatility index(PI) and systolic diastolic ratio(SDr) were measured for diagnosis of obstructed urinary tract. RI, PI and SDr were a measure of intrarenal blood flow impedance. This study was consisted of 2 groups. The normal group was studied in 16 normal adult dogs and the study group was studied 7 dogs with surgically induced, unilateral ureteral obstruction. In the study group, parameters were checked in normal condition and on 1, 2, 3, 5, 7 and 10th day after ligation. The result were summarized as follows. In the normal group, RI, PI and SDr of the left kidney was $0.65{\pm}0.04$, $1.25{\pm}0.12$ and $292.45{\pm}29.40$, respectively. RI, PI and SDr of the right kidney were $0.64{\pm}0.05$, $1.28{\pm}0.20$ and $282.25{\pm}37.26$, respectively. In the study group, RI of the left kidney induced ligation was increased significantly on 1, 2, 3, 5, 7 and 10th day. RI of the left kidney on 1, 2, 3, 5, 7 and 10th day were $0.75{\pm}0.05$, $0.71{\pm}0.03$, $0.74{\pm}0.04$, $0.74{\pm}0.02$, $0.73{\pm}0.02$ and $0.73{\pm}0.04$, respectively. PI of the left kidney was increased significantly on 1, 3, 5 and 7th day. PI of the left kidney on 1, 3, 5 and 7th day were $1.57{\pm}0.21$, $1.54{\pm}0.24$, $1.60{\pm}0.15$ and $1.60{\pm}0.26$, respectively. SDr of the left kidney increased significantly on 1, 2, 3, 5 and 7th day. SDr of the left kidney on 1, 2, 3, 5 and 7th day were $412.18{\pm}86.69$, $352.14{\pm}47.05$, $399.77{\pm}65.54$, $369.43{\pm}48.34$ and $365.57{\pm}22.46$, respectively(p<0.05). In the study group, RI of the left kidney was more increased than that of the right kidney on 1, 2, 3, 5, 7 and 10th day. PI of the left kidney was more increased than that of the right kidney on 1, 3, 5, and 7th day. SDr of the left kidney was more increased than that of the right kidney on 1, 2, 3, 5 and 7th day(p<0.05). RI was effective in the diagnosis of an acute unilateral ureteral obstruction. PI and SDr were insufficient in the diagnosis of an acute unilateral ureteral obstruction.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.55-63
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• 1997

The present study was designed to quantify the alterations of renal renin, angiotensin type I receptor ($AT_1$), $TGF-{\beta}1$, and fibronectin gene expression in rats with unilateral ureteral obstruction (UUO). We also investigated the change of $AT_1$ density during UUO. Reverse transcription-polymerase chain reaction (RT-PCR) technique and receptor binding assay were used to detect mRNA expression and receptor density, respectively. At one day after UUO, renin mRNA level of the obstructed kidneys was decreased transiently and then subsequently increased to the level of sham kidneys. In the contralateral kidneys of the same rats, on the contrary, renin mRNA level was gradually decreased. Then, at 9 days after UUO, it was significantly lower than that of sham kidneys. The expressions of both $AT_1$ subtypes, called $AT_{1A}$ and $AT_{1B}$, mRNAs did not change at any time. UUO led to a significant decrease in $AT_1$ density in the obstructed kidneys compared with the sham kidneys at 1 and 3 days $(66\;{\pm}\;11.6%\;(p<0.005)\;and\;73\;{\pm}\;4.0%$ (p<0.01), respectively). Thereafter, $AT_1$ density was gradually increased and at 9 days it showed a marked elevation in the obstructed kidneys compared to the sham kidneys. In contrast, in the contralateral kidneys $AT_1$ density was significantly reduced from 3 to 9 days after UUO. The $TGF-{\beta}$1 mRNA level of the obstructed kidneys was unexpectedly decreased at 6 days after UUO. Then, at 9 days it was followed by a significant increase in the obstructed kidneys, whereas it showed an obvious decrease in the contralateral kidneys. In addition, fibronectin mRNA level was also significantly increased in the obstructed kidneys after UUO compared to the sham or the contralateral kidneys of the same rats. These results suggest a differential regulation of renal renin, $AT_1$ receptor, $TGF-{\beta}$1 and fibronectin mRNA levels at different stages of UUO.

• Biomolecules & Therapeutics
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• 제29권1호
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• pp.41-51
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• 2021

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson's trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

• Childhood Kidney Diseases
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• 제6권1호
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• pp.85-91
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• 2002

서 론 : Phosphodiesterase (PDE) 억제제는 세포내 cAMP를 증가시키며, cAMP는 TGF-${\beta}1$에 의한 connective tissue growth factor (CTGF)의 발현을 억제하는 것으로 알러져 있다. 그러므로 저자들은 PDE 억제재가 TGF-${\beta}1$의 변화 없이 긴 섬유화를 억제할 수 있는지를 확인해 보고자 본 연구를 시행하였다. 방 법 : 백서에서 일측성 요관 결찰로 신 간질 섬유화를 유발하였다. 실험군에서는 PDE3 억제제인 cilostazol (1 g/L)이나 PDE5, PDE6, PDE8의 hybrid 억제제인 dipyridamole (750 mg/L)이 첨가된 음료수를 공급하였다. 일주일 후 신장을 적출하여 Masson-trichrome score를 평가하고, 신조직 조건배지에서 fibronectin과 TGF-${\beta}1$을 ELISA법으로 정량하였다. 결 과 : 대조군에 비해 cilostazol 군에서 Masson-trichrome score와 신조직 조건배지의 fibronectin 농도가 유의하게 낮았다(P<0.05). Dipyridamole군의 Masson-trichrome score와 조건배지의 fibronectin 농도도 대조군에 비해 낮아 보였으나 통계적 유의성을 보여주지 못했다. 신조직 조건배지의 TGF-${\beta}1$ 농도는 대조군, cilostazol군, dipyridamole군간에 차이가 없었다. 결 론 : 선택적 PDE3 억제제인 cilostazol은 TGF-${\beta}1$의 억제에 의존하지 않고 일측성 요로 폐쇄에 의한 신 섬유화를 억제하였다.