• Journal of Nutrition and Health
• /
• 제53권1호
• /
• pp.1-12
• /
• 2020

본 연구에서는 고혈당으로 인해 유발되는 당뇨병성 신장병증의 대표적인 증상인 사구체 경화증을 완화시키는 nobiletin의 효능에 대해 알아보고자 하였다. 신장 세포인 HRMC를 이용하여 고혈당에서의 세포외 기질 축적 단백질의 발현과 경화에 관여하는 신호 전달 억제 효능을 확인한 결과 nobiletin은 고혈당의 자극에 의해 증가하는 섬유화 단백질인 collagen IV, fibronectin 그리고 CTGF의 발현을 억제하였으며, 여기에 관여하는 TGF-β1-Src-caveolin-1 신호 전달 경로를 통해 사구체 경화증을 억제하는 것을 확인하였다. 따라서 nobiletin은 고혈당으로 유도된 당뇨병성 신장병증에 있어 사구체 경화증을 예방하는 기능성 성분으로서의 활용 가능성을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권6호
• /
• pp.485-489
• /
• 2015

Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidney, but the efficacy of currently available strategies for the prevention of DN remains unsatisfactory. In this study, we investigated the effects of free anthraquinones (FARs) extract, which was extracted from the rhubarb and purified by macroporous resin DM130 with gradient mixtures of ethanol/water as the lelution solvents, in high glucose-cultured glomerular mesangial cells (MCs). The cell proliferation was determined by CCK-8 assay, the levels of TGF-${\beta}1$, CTGF, ColIV and FN proteins in the supernatant of MCs were measured by ELISA assays, and the mRNA levels of these four genes were detected by RT-PCR. The results showed that the increased proliferation of MCs, the mRNA levels and protein expression of TGF-${\beta}1$, CTGF, ColIV and FN induced by high glucose were inhibited after the treatment with the FARs extract. This indicated that FARs extract could inhibit cell proliferation and the expression of main extracellular matrix induced by high glucose in MCs. The FARs extract exhibited potential values for prophylaxis and therapy of DN.

• The Korean Journal of Physiology and Pharmacology
• /
• 제11권4호
• /
• pp.145-148
• /
• 2007

Gynura procumbens (Lour.) Merr. has been used in some parts of Southeast Asia as a folk medicine to treat kidney diseases, diabetes mellitus, and hyperlipidemia. The present work was undertaken to prove the mechanisms of G. procumbens in the management of glomerular diseases. We investigated the effect of an aqueous extract of G. procumbens on cell proliferation, DNA synthesis, and the expressions of $TGF-{\beta}1$, PDGF-BB, CDK1, CDK2, and CDK4 in fetal bovine serum-activated human mesangial cells (MCs). The G. procumbens extract inhibited proliferation, DNA synthesis, expressions of PDGF-BB, CDK1, and CDK2 mRNA, and expression of $TGF-{\beta}1$ protein in MCs. The inhibitory effect of G. procumbens on MC proliferation may be mediated by suppression of PDGF-BB and $TGF-{\beta}1$ expressions and the modulation of CDK1 and CDK2 expression. Therefore, G. procumbens shows promise as an adjunct therapy in preventing progressive renal diseases.

• Applied Microscopy
• /
• 제27권4호
• /
• pp.391-402
• /
• 1997

본 연구는 고단백뇨를 보이는 신장질환모델마우스(FGS/Kist mouse)의 사구체에 대한 미세구조학적 변화를 관찰하고자 수행하였다. 전반적으로 사구체내의 모세혈관은 주변부의 혈관사이세포(mesangial cell) 부위의 확장으로 인하여 관강이 좁아져 있었으며 관강내에는 점액양 물질들이 흔히 관찰되었다. 또한 사구체바닥판(basal lamina)이 모세혈관 사이의 공간쪽으로 돌출되어져 있는 소견들도 볼 수 있었다. 혈관사이세포 부위에는 주변부와 뚜렷이 구분되는 전자밀도가 높은 물질들이 많이 차여져 있었다. 한편, 사구체바닥판에 인접하여 존재하고 있는 발세포들(podocytes)은 세포질내 많은 공포들이 관찰되었고, 발세포들이 내고 있는 발세포발(foot process)들은 서로 융합되거나 소실되어 매우 불규칙적인 소견을 보였다.

• Molecules and Cells
• /
• 제38권4호
• /
• pp.285-296
• /
• 2015

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-${\beta}$. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

• Childhood Kidney Diseases
• /
• 제20권2호
• /
• pp.83-87
• /
• 2016

Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease that is difficult to diagnose. CLD requires early treatment to correct electrolyte imbalance and alkalosis and to prevent severe dehydration. Renal injury is clearly associated with defective electrolyte balance induced by CLD, particularly during the first months or years of life. A 7-year-old boy was diagnosed with CLD following detection of a homozygous mutation (c.2063-1G>T) in SLC26A3 at 6 months of age. During treatment with electrolyte supplements, mild proteinuria was detected at 8 months of age, and is still present. Renal biopsy showed the presence of focal renal dysplasia, with metaplastic cartilage and mononuclear cell infiltration, calcification, and fibrosis in the interstitium. Up to two-thirds of the glomeruli exhibited global obsolescence, mostly aggregated in the dysplastic area. In nondysplastic areas, the glomeruli were markedly increased in size and severely hypercellular, with increased mesangial matrix, and displayed segmental sclerosis. The marked glomerular hypertrophy with focal segmental glomerulosclerosis suggested a compensatory reaction to the severe nephron loss or glomerular obsolescence associated with renal dysplasia, with superimposed by CLD aggravating the tubulointerstitial damage.

• Applied Microscopy
• /
• 제17권1호
• /
• pp.47-64
• /
• 1987

Morphological difference of the renal glomerulus at different age groups have been studied in young (three month-old), adult (twelve month-old) and old (thirty month-old) Fisher strain 344 rats. Pieces of the tissues were taken from renal corticies prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde (0.1 M Millonig's phosphate buffer, pH 7.3), following by post-fixation with 1% osmium tetroxide (0.1 M Millonig's phosphate buffer, pH 7.3) and embedded within Araldite. The ultrathin sections contrasted with uranyl acetate and lead citrate were observed under a JEM 100CX electron microscope. The mean thickness of glomerular basal lamina and Bowman's capsule were determined by measuring the thinnest portion of basal lamina, and by taking the average of 50 readings from electron micrographs at different ages. The numerical changes of the slit pores were compared based upon the numbers over the length of 10um of glomerular basal lamina. The results were as follow: 1. The thickness of glomerular basal lamina is increased during aging; 140.4 nm in young rats, 270.0 nm in adult ones, and 437.8 nm in old ones. 2. The thickness of basal lamina of parietal cells of Bowman's capsule is 187.5 nm in young rats, 914.0 nm in adult ones, and 2850.0 nm in old ones. 3. The numbers of the slit pores of basal lamina are reduced during aging, 30.3 slit pores/$10{\mu}m$ in adult ones, and 24.2 slit pores/$10{\mu}m$ in old ones. 4. Accumulation of dense intracytoplasmic filamentous material in the parietal cells of Bowman's capsule is increased in the vicinity of the basal lamina during aging. The proximal tubule-like epithelial cell in Bowman's capsule is observed at one glomerulus in a young rat. 5. The endothelial cells are edematous and form balloon-like structure protruding into capillary lumen in young and old rats. 6. Cytoplasm of the podocyte shows a variety of alteration during aging, such as swelling of mitochondria and of endoplasmic reticulum, and increase of microtubules, microfilaments, lysosomes and lamellated myelin structures, etc. Accumulation of dense intracytoplasmic material in the foot processes is increased in the vicinity of the basal lamina during aging. The podocytic membrane-like structures are seen in young and o]d rats. 7. The mesangial matrices and mesangial cells are increased during aging, and slight swelling of endoplasmic reticulum and Golgi cisternae in young and old rats.

• Applied Microscopy
• /
• 제27권4호
• /
• pp.373-389
• /
• 1997

Morphological difference of the renal glomerulus at different age groups have been studies in one week-old, five weeks-old, eight weeks-old, six months-old, twelve months-old, eighteen months-old, twenty-four months-old, and thirty months-old ICR mice. Pieces of the tissue taken from the renal corticies were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde solution (0.1 Millonig's phosphate buffer pH 7.3), and 1% osmium tetroxide solution (0.1 M Millonig's phosphate buffer, pH 7.3), and were embedded in araldite mixture. The ultrathin sections were stained with uranyl acetate and lead citrate solution, and were observed under a JEM 100CX-II electron microscope. The results were as follows: 1 In the one week-old mouse, thicknesses of the three layers of the glomeluar basal lamina (lamina densa, lamina rara interna and lamina rara externa) are similar, but in the five weeks-old mouse, thick lamina densa becomes a greater portion of the thickness of whole glomerular basal lamina. 2. No difference was noticed between thickness of the renal glomerular basal lamina of the five weeks-old mouse compare with that of the one week-old one, but basal lamina of the eight weeks-old one is thickened considerably and thicknesses were maintained through twelve months-old one. After eighteen months, the thickness of the glomerular basal lamina is increased remarkably. 3. After eighteen months, electron dense deposits within the basal lamina of the renal glomeruli are observed frequently. 4. Amount of the microfilaments in the mesangial cells and the mesangial matrices are increasing during aging. 5. The thicknesses of the basal laminae of the Bowman's capsule are increasing during aging. 6. After twenty four months, the proximal tubular cell-like parietal cells with well developed microvilli are observed frequently. From the above results, it was suggested that the renal glomerulus matures structurally in five weeks, and the function of the glomerulus is suppressed after eighteen months.

• Applied Microscopy
• /
• 제27권4호
• /
• pp.433-452
• /
• 1997

Mongolian gerbil (Meriones unguiculatus) has been as an animal model for studing the neurological diseases such as stroke and epilepsy because of the congenital incompleteries in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animals. In order to accomplish the this research, first of all another divided the laboratory animals 5 groups of which each group include the 5 animals. In this study were investigated the histological structure in the kidney, measured the plasma osmolalities at the time of sacrifice of indivisual animals, and the body weights every day during water-deprived. The results obtained in this study were summarized as followings: 1. The body weights and decreasing rates of the body weight in water-deprived mongolian gerbil groups were continuosly decreased. 2. The plasma osmolalities were increased from the 5th water-deprived day, after then the gradually increasing reached nearly its equilibrium state at the 10th water-deprived day. 3. The urine volumes were abruptly decreased from the 2th water-deprived day, after then the gradually decreasing patterns were reached nearly its equilibrium state at the 10th day, and stopped the 11th day. 4. In the light microscopical observation of the kidney, glomerular capillary loop thickening, mesangial matrix increasing, sclerosis, glomerular cystic atrophy, interstitial fibrosis, tubular dilatation, mononuclear interstitial inflammation, interstitial mineralization, and hyperplasia of the collecting duct epithelium in the cortex area, were observed from the 10th water deprived day, and the lesions were gradually severe changed as the time lapse. 5. In the electron microscopical findings of the kidney, the degenerative changes of endothelial cell, podocyte and mesangial cell in glomeruli were initially observed on the 10th water-deprived day as well as the degeneration of microvilli and intracellular organelle in the renal tubules.

• Childhood Kidney Diseases
• /
• 제16권1호
• /
• pp.21-31
• /
• 2012

초점성 분절성 사구체 경화증(focal segmental glomerulosclerosis; FSGS)은 경화증을 주 병변으로 하는 질환으로서 일차성 사구체 질환의 하나이면서 진행된 사구체 질환의 형태적 변화를 기술하는 단어로도 사용되고 있다. 사구체에는 경화증, 유리질 형성, 거품세포의 출현, 발세포의 공포화, 광륜형성 등이 보이고, 간질의 섬유화와 염증세포의 침윤, 세뇨관의 위축, 혈관의 비후 및 내막 섬유화 등을 특징으로 한다. 면역형광검사에서 부분적으로 IgM과 C3 등의 침착을 보이지만 면역관련 질환은 아니다. 전자현미경 검사에서는 발세포의 손상 현상으로 세포질 내의 공포화와 족돌기가 상실되는 것이 중요 소견이다. 2004년 표준화 된 FSGS의 분류는 과거의 형태학적 변형들을 모아서 임상과의 상관관계를 지웠다. 그 결과 tip형이 가장 예후가 좋으며, collapsing형이 가장 나쁜 것으로 알려졌다. 그러나 이 분류가 증례에 따라서는 적용하기가 애매한 경우가 많고, collapsing형을 FSGS에 분류하는 것에 대한 반론 등이 제기되고 있다. 한편, 임상적으로는 FSGS를 원인에 따라 분류하여 거꾸로 형태학적 공통점을 찾으려는 노력을 하고 있다. 사구체의 수가 적어서 일어나는 과여과로 인한 FSGS는 perihilar형이 많고 유전적 질환에 의한 것은 diffuse mesangial sclerosis가 특징인 것으로 주장되고 있다. FSGS는 이와 같이 아직도 밝혀져야 할 것이 많은 질환이며, 계속적인 연구가 이루어져야 할 필요가 있다.