• Title/Summary/Keyword: Collagen IV

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The Effects of Gypsum Fibrosum on Renal Functional and Histopathological Disorder in Chronic Renal Failure Rat Model (석고(石膏)가 만성 신부전 Rat의 신기능 보호 및 조직학적 변화에 미치는 영향)

  • Byun, Sang-Hyuk
    • The Journal of Internal Korean Medicine
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    • v.29 no.4
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    • pp.871-886
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    • 2008
  • Objective : Gypsum fibrosum has been traditionally used in treatment of febrile diseases and recently been shown to have anti-inflammatory effect. Chronic renal failure has a serious clinical symptoms including proteinuria, azotemia, anemia, and hyperlipidemia and has characteristic histopathological changes, glomerular hypertrophy, infiltration of inflammatory cells, and crescentic sclerosis, We investigated the effects of gypsum fibrosum on renal functional and histopathological disorder in chronic renal failure rat model induced 5/6 nephrectomy. Methods : Using Sprague-Dawley rats, CRF was induced by 5/6 nephrectomy. The rats were divided into 3 groups, normal, conrol, and gypsum administered orally with gypsum fibrosum 500mg/kg/day. Body weight, 24 hr proteinuria, hematologic analysis, and histological morphologic changes were followed up after 8 weeks. The glomerular macrophage/monocyte infiltration, $TGF-{\beta}_1$, type IV collagen, and angiotensin II type1 receptor($AT_1$) were evaluated by immunohistochemistry. Resuls : In the CRF control group, functional parameters and histopathologic changes clearly indicated the development of CRF. 24 hr proteinuria significantly increased in the CRF control group over the normal group, and serum creatinine level was lower in the gypsum group than in the control group, LDL-cholesterol was significantly lower in the gypsum group than in the control group. Morphological investigations showed a variety of characteristic features of CRF, glomerular hypertrophy, increasing cellular density of glomerulus, deposition of extra-cellular matrix, fibrotic change, and glomerular sclerosis in the control group, but in the gypsum group, these features diminished significantly. In observation of renal type IV collagen and $AT_1$ expression, positive area significantly increased in the control group over the normal group, and it significantly decreased in the gypsum group compared to the control group. Conclusions : Our findings suggest that gypsum fibrosum inhibits $AT_1$ and type IV collagen expression in renal tissues and attenuates progression of glomerulosclerosis and interstitial fibrosis in chronic renal failure rats, which lead to amelioration of renal function. From these results, we suggest that gypsum fibrosum may have renoprotective effects and could be a useful remedy agent for treating chronic renal failure.

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The Effects of Salvia Miltiorrhiza on Renal Function and Histopathological Changes in Streptozotocin-induced Diabetic Nephropathy Rat Model (단삼이 당뇨병성 신병증 Rat의 신기능 및 조직학적 변화에 미치는 영향)

  • Kim, Young-Seok;Lee, Byung-Cheol;Ahn, Se-Young;Doo, Ho-Kyung;Ahn, Young-Min
    • The Journal of Internal Korean Medicine
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    • v.29 no.3
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    • pp.787-799
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    • 2008
  • Objective : Diabetic nephropathy is the most common cause of end stage renal disease. AGE, $TGF-{\beta}1$ type IV collagen, and macrophage/monocyte infiltration are the main factors of diabetic nephropathy. We investigated the effects of Salvia miltiorrhiza on renal function and histopathological changes in streptozotocin(STZ)-induced diabetic nephropathy rat model. Methods : Diabetes was induced in male Sprague-Dawley rats(290${\pm}$10g) by injecting STZ(45mg/kg) into the tail vein. Rats were divided into 3 groups(n = 6): normal, control, and salvia. After 8 weeks of administration of Salvia miltiorrhiza extract on the Salvia group, we checked 24 hrs urine, blood biochemistry and renal tissue to evaluate renal function and histopathological changes by examining parameters including albuminuria, BUN, creatinine, cholesterol, LDL, TG, macrophage/monocyte antigen(ED-1), $TGF-{\beta}1$, AGE, and type IV collagen. Results : Salvia miltiorrhiza decreased the amount of 24hrs proteinuria, and inhibited histopathological changes of diabetic nephropathy including the expression and accumulation of various factors which could promote development of diabetic nephropathy. Conclusion : These findings suggest that Salvia miltiorrhiza might protect the renal function and inhibit the development of renal injury by regulating factors including AGE, $TGF-{\beta}1$ Type IV collagen, macrophage and monocyte infiltration. So Salvia miltiorrhiza can be used for diabetic patients to prevent the progression of diabetic nephropathy.

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De novo mutations in COL4A5 identified by whole exome sequencing in 2 girls with Alport syndrome in Korea

  • Han, Kyoung Hee;Park, Jong Eun;Ki, Chang-Seok
    • Clinical and Experimental Pediatrics
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    • v.62 no.5
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    • pp.193-197
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    • 2019
  • Alport syndrome (ATS) is an inherited glomerular disease caused by mutations in one of the type IV collagen novel chains (${\alpha}3$, ${\alpha}4$, and ${\alpha}5$). ATS is characterized by persistent microscopic hematuria that starts during infancy, eventually leading to either progressive nephritis or end-stage renal disease. There are 3 known genetic forms of ATS, namely X-linked ATS, autosomal recessive ATS, and autosomal dominant ATS. About 80% of patients with ATS have X-linked ATS, which is caused by mutations in the type IV collagen ${\alpha}5$ chain gene, COL4A5. Although an 80% mutation detection rate is observed in men with X-linked ATS, some difficulties do exist in the genetic diagnosis of ATS. Most mutations are point mutations without hotspots in the COL4A3, COL4A4, and COL4A5 genes. Further, there are insufficient data on the detection of COL4A3 and COL4A4 mutations for their comparison between patients with autosomal recessive or dominant ATS. Therefore, diagnosis of ATS in female patients with no apparent family history can be challenging. Therefore, in this study, we used whole-exome sequencing (WES) to identify mutations in type IV collagen in 2 girls with glomerular basement membrane structural changes suspected to be associated with ATS; these patients had no relevant family history. Our results revealed de novo c.4688G>A (p.Arg1563Gln) and c.2714G>A (p.Gly905Asp) mutations in COL4A5. Therefore, we suggest that WES is an effective approach to obtain genetic information in ATS, particularly in female patients without a relevant family history, to detect unexpected DNA variations.

Anti-platelet and Anti-thrombotic Effects of Gastrodia elata (천마(Gastrodia elata Blume)의 항혈소판, 항혈전활성)

  • Paik, Young-Sook;Song, Jae-Kyoung;Yoon, Chun-Hee;Chung, Kyo-Soon;YunChoi, Hye-Sook
    • Korean Journal of Pharmacognosy
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    • v.26 no.4
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    • pp.385-389
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    • 1995
  • MeOH extract of Gastrodia elata was fractionated to five solvent fractions, hexane fr (fr I), 90% MeOH fr (fr II), EtOAc fr (fr III), BuOH fr (fr IV) and $H_2O$ fr (fr V). Among the five fractions, fr II, III and IV showed platelet anti-aggregating effects against ADP or collagen induced rat platelet aggregation in vitro. Fr II , III and IV were also tested in vivo, in the mouse and rat models of thrombosis. Oral administration of fr II, III or IV enhanced the recovery from the thrombotic shock in the mouse model of thrombosis to 32-40% from 17% of recovery with the control group of mice. Treatment with fr II, III or IV also attenuated the sudden reduction in the blood platelet count following intravenous collagen injection to rat. The above results were indicative of the presence of anti-platelet and anti-thrombotic components in this plant.

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[Secondary publication] Sudden Aortic Rupture in Ehlers-Danlos Syndrome Type IV (엘러스-단로스 제4형 증후군 환자에서 발생한 대동맥 파열)

  • Baek, Taehwa;Kim, Minjung;Ki, Chang-Seok;Park, Seong Hwan;Lee, Heon;Kim, Kyung Ryoul;Choi, Byung-Ha
    • The Korean Journal of Legal Medicine
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    • v.40 no.2
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    • pp.61-64
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    • 2016
  • Ehlers-Danlos syndrome type IV (EDS IV) is a hereditary disorder of the connective tissue, characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations of the gene for type III procollagen (COL3A1), resulting in insufficient collagen production or a defect in the structure of collagen. EDS IV can have fatal complications such as the rupture of great vessels or organs, which can cause hemorrhaging and sudden unexpected death. Here, we report a case of a 43-year-old female who collapsed after a struggle with a neighbor. In this patient, the bifurcation of the bilateral common iliac artery ruptured, with no evidence of trauma, inflammation, or atherosclerosis. Genetic analysis of COL3A1 showed the presence of a c.2771G>A (p.Gly924Arg) mutation, which may be associated with EDS IV. The forensic pathologist should consider the possibility that the spontaneous visceral or arterial rupture was caused by EDS IV. Genetic analysis is not currently a routine procedure during autopsy. However, in this case, we suggest that the patient possibly had an underlying EDS IV condition, and we recommended family members of the deceased to seek genetic analysis and counseling.

Electron Microscopic Studies on Distribution of Collagen IV of Lens Capsule and Apoptosis of Lens Epithelium in Age-related Cataractous Human (백내장 환자의 연령에 따른 수정체낭 Type IV 아교섬유의 분포와 수정체낭 상피세포 자연사 및 전자현미경적 변화에 대한 연구)

  • Heo, Jun;Yang, Young-Chul;Won, In-Gun
    • Biomedical Science Letters
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    • v.4 no.2
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    • pp.77-86
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    • 1998
  • Age-related changes in the lens capsule and epithelium of cataractous patients, ranging from 20 to 7o years old, were studied by means or LM, immunohistochemistry, and TEM. The lens capsule was divided into four zones; the anterior, subanterior, middle, and basal zone. The van Gieson staining reaction for collagen was prominent at the anterior and subanterior parts of the lens capsule. The reaction was more decreased in the elder group than the younger group. The collagen type IV reaction was prominent at the anterior zone of the lens capsule and around the cell. The reaction was more decreased in the elder group than the younger group. 3. The Periodic Acid Shiff-Alcian Blue reaction for mucopolysaccharide was prominent at the anterior zone of the lens capsule. The reaction was more decreased in the elder group than the younger group. The Apoptotic reaction was prominent at the nucleus of the lens epithelial cell. In the elder the cataractous group, the number of the apoptotic cells was more decreased. The electron microscopic change of lens epithelial cells were characterized by the increase of lateral fold and the cytoplasm with various vacuoles and Golgi complex. In the basal part, lens epithelial cell protruded toward the lens capsule in the 20-year-old group. The basal part of the 40-year-old group was flattened and covered with the cytoplasmic processes of adjacent cells. In the 60-year-old group, the mass of rough filaments separated lens capsule and the basal part of the lens epithelial cell. The electron microscopic change of the middle part of lens capsule was characterized by the aggregation of electron dense materials in the 40-year-old group, and the appearance of filamentous materials and the decrease of electron dense granules in the 60-year-old group.

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A COMPARATIVE STUDY OF WOUND HEALING AFTER SKIN INCISION WITH SCALPEL, $CO_2$, AND Nd:YAG LASER IN RATS (수술칼, $CO_2$ 및 Nd:YAG 레이저에 의한 절개 창상의 치유에 관한 비교 연구)

  • Choi, Jae-Sun;Ryu, Sun-Youl
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.22 no.1
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    • pp.33-42
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    • 2000
  • The purpose of this study was to compare the wound healing process after skin incision using scalpel, $CO_2$ laser and pulsed Nd:YAG laser in rats. After skin on the back was incised 3 cm long, rats were sacrificed at 1, 3, 7, 14, 21 and 28 days. Macroscopic, histologic and immunohistochemical examinations using the collagen type IV and the CD34 antibodies which are necessary to the forming process of new capillary were performed. Results obtained were as follows ; Macroscopically the initial wound healing of the laser group was about $1{\sim}2$ weeks slower than that of the scalpel group. There weren't however any remarkable differences in all groups in 4 weeks after incision. By histologic finding, acute inflammatory cells were more prominent during the initial wound healing in the scalpel group than in the other groups. Epithelialization started in the order of scalpel, $CO_2$ and Nd:YAG laser group after skin incision. By the Masson's trichrome stain, collagen synthesis in the Nd:YAG laser group was more slowly initiated than in the other groups. But it was completed at the $3{\sim}4$ weeks in all groups. Immunohistochemically, collagen type IV and CD34 expression were markedly increased at 2 weeks in the scalpel and $CO_2$ laser group. Meanwhile, in the Nd:YAG laser group, these reactions were observed later tan the other groups. Collagen type IV and CD34 expression were decreased in all groups after 4 weeks. These results suggest that $CO_2$ and Nd:YAG laser showed similar healing process compared with scalpel and a potential substitute for scalpel in skin incision.

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The Effect of Behavioral Response and Arthritic Tissue on Swimming Exercise and Achyranthes Radix Extracts in Type II Collagen-Induced Arthritic Rat (제 2형 콜라겐 유도 관절염에서 수중운동과 우슬추출물이 행동반응과 관절 조직에 미치는 영향)

  • Choi, Ki-Bok;Kim, Gye-Yeop;Nam, Ki-Won;Kim, Kyong-Yoon;Kim, Eun-Jung
    • The Journal of Korean Physical Therapy
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    • v.21 no.2
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    • pp.117-124
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    • 2009
  • Purpose: This study examined the effects of swimming exercise and Achyranthes Radix extracts on the inflammatory and behavioral responses in type II collagen-induced arthritic rats for 28 days. Methods: Sprague-Dawley rats were allocated randomly to one of the following four groups: only type II collageninduced (group Ⅰ), application of swimming exercise after type II collagen-induced (group II), application of Achyranthes Radix ointment after type II collagen-induced (group III), application of swimming exercise and Achyranthes Radix ointment after type II collagen-induced (group IV). Arthritis was established in SD rats by an intradermal injection of Chick type II collagen plus incomplete Freund's adjuvant at the base of the tail of the animals. The swimming exercise program consisted of a 25 min swimming session/day with a load corresponding to 5.5% of the weight bearing, three days/week for four weeks. The Achyranthes Radix ointment (0.1g) was applied twice a day for five days. The changes in behavior, H & E stain, and cyclooxygenase-2 (COX-2) level in the knee joint were assessed. Results: The gross and histological examination, after RA induction showed reddening, edema and erythema. The H & E stain revealed the destruction of articular cartilage, bony erosion and the infiltration of inflammatory cells after RA induction. The mechanical allodynia test results were significantly higher in group I than in groups II, III and IV (p<0.01). The immunohistochemistrical response of COX-2 in the knee joint showed that groups II, III, IV had a lower response effect than group I. Conclusion: Swimming exercise training and Achyranthes Radix ointment decreased the inflammatory responses and enhanced the behavioral responses in the arthritic rats.

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양성 성대질환의 콜라겐 발현 및 분포양상

  • 손영익;고영혜;고석주
    • Proceedings of the KSLP Conference
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    • 1997.11a
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    • pp.263-263
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    • 1997
  • 성대결절, 폴립, 부종 등은 성대의 남용이나 과용등의 성대손상이 그 공통된 주된 원인으로 거론되고 있다. 하지만 음성치료를 비롯한 보존적 치료에 대한 반응이 서로 상이하며, H&E 염색을 이용한 병리조직학적인 감별이 곤란하여 진단에 혼돈이 있으며, 치료의 방침을 결정하거나 예후를 예측함에 있어서도 어려움이 있다. 양성성대질환은 기저막부 위와 세포외 간질에 주된 변화가 발생함이 알려져 있고, collagen type IV의 발현양상이 성대결절과 폴립에서 서로 다름에 대하여는 보고된 바 있으나 기타 점막하층의 골격유지를 주기능으로 하는 대표적 세포외간질인 collagen subtype에 대하여는 아직 보고된 바가 없는 실정이다. Collagen 발현의 차이를 연구하는 것은 상기질환의 병인을 이해하고 질환분류의 guideline을 제시하며 나아가 적절한 치료방범을 제시하는 데에 큰 의미가 있을 것으로 기대된다. Paraffin에 고정되어 있는 5례 이상씩의 성대결절과 성대폴립, 육아 종 및 라인케씨 부종 조직을 collagen type I부터 VII에 대하여 peroxidase kit를 사용하여 염색한 후 각 군간에 collagen 분포양상과 발현정도에 차이가 있는가 비교하였다.

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Peroxidase Activity of Peroxidasin Affects Endothelial Cell Growth (내피 세포 성장에 영향을 미치는 PXDN의 peroxidase 활성)

  • Kyung A Ham;Seong Bin Jo;Min Ju Lee;Young Ae Joe
    • Journal of Life Science
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    • v.33 no.1
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    • pp.8-14
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    • 2023
  • Peroxidasin (PXDN), a multidomain heme peroxidase containing extracellular matrix (ECM) motifs, as well as a catalytic domain, catalyzes the sulfilimine crosslink of collagen IV (Col IV) to reinforce Col IV scaffolds. We previously reported that PXDN is required for endothelial cell (EC) survival and growth signaling through sulfilimine crosslink-dependent matrix assembly. In this study, we examined whether peroxidase activity is required for PXDN function in ECs. First, we constructed a mutant PXDN by point mutation of two highly conserved amino acids, Q823 and D826, which are present in the active site of the peroxidase domain. After isolation of HEK293 clones highly expressing the mutant protein, conditioned medium (CM) was obtained after incubating the cells in serum-free medium for 24 hours and then analyzed by Western blot analysis under nonreducing conditions. The results revealed that the mutant PXDN formed a trimer and that it was cleaved by proprotein convertase-like wild-type (WT) PXDN. However, peroxidase activity was not detected in the CM containing the mutant PXDN, in contrast to that of WT PXDN. In addition, the sulfilimine crosslink ability of the mutant PXDN was lost. Moreover, the CM containing the mutant PXDN failed to promote the growth of PXDN-depleted ECs, unlike the CM containing WT PXDN. These results suggest that the peroxidase activity of PXDN affects EC growth by forming a sulfilimine crosslink.