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섬유아세포의 증식과 Collagen 합성에 대한 Prostaglandin E2 의 조절작용
김인산,조준승 ( In Sam Kim,Joon Seung Jo ) 생화학분자생물학회 1990 BMB Reports Vol.23 No.1
PGE₂ has been known to modulate diploid human fibroblast proliferation and collagen production by intracellular cyclic AMP mediated pathway but it still remains unclear that the suppressive effect of PGE₂ on proliferation and collagen synthesis are mediated by the elevated intracellular cyclic AMP levels. The purpose of present study was to determine the effects of PGE₂, db-cAMP or cholera toxin on cell proliferation and collagen production and to study how the temporal changes of intracellular cyclic AMP levels caused by PGE₂ are associated with cell proliferation and collagen production. And we also hypothesized that lengthy exposure of fibroblast cultures to prostaglandins could lead to overgrowth of the insensitive cells which might be responsible for fibrotic diseases. At least, 48 hours of incubation were required to suppress the cell proliferation by PGE₂, and under the same conditions there were no changes of intracellular cyclic AMP levels during 72-hour incubation of PGE₂. 48- and 72-hour incubation of PGE₂ showed dose- and time-dependent suppression of the cell proliferation. Dibutyryl cyclic AMP and cholera toxin appeared to suppress cell proliferation by even 24 hours incubation and they also showed dose- and tme-dependent suppression of the cell proliferation. Cholera toxin increased intracellular cyclic AMP levels maximally after one hour and then decreased its level but still maintained its elevated state for 24 hours. Short-term incubation of dibutyryl cyclic AMP or cholera toxin for six hours wass enough to suppress the cell proliferation. Total protein and collagen production were suppressed by PGE₂, dibutyryl cyclic AMP or cholera toxin in a dose-dependent manner and their effects seemed to be associated with intracellular cyclic AMP levels which were elevated by PGE₂ or cholera toxin. One hour incubation of PGE₂ was enough to suppress total protein and collagen production by fibroblasts. Judging by the fact that treatment of PGE₂ or dibutyryl cyclic AMP decreased the steady state levels of mRNAs for procollagens and fibronectin and that co-treatment with actinomycin D didn`t show any difference in the steady state levels of each mRNA, the inhibitory actions of PGE₂ and dibutyryl cyclic AMP on the fibronectin and collagen production seem to occur at transcriptional level. Long-term exposure for PGE₂ could result in selection of subpopulation of fibroblasts which showed less responsiveness to reexposure of PGE₂ in the cell proliferation but not in collagen production. These results indicate that prostaglandin E₂ could suppress the proliferation of human fibroblast cells by cyclic AMP-independent events and by which some subpopulations of fibroblasts might be selected to overgrow when exposed to PGE₂ for a long time and also indicate that PGE₂ could suppress total protein and collagen production at the transcriptional level by cyclic AMP-dependent events.
일반연제 발표 : 저 포도당 대사산물 복막투석액의 사용이 복막염증, 복막의 구조적 변화 및 복막 혈관생성 지표들에 미치는 영향
김찬덕 ( Kim Chan Deog ),김용림 ( Kim Yong Lim ),도준영 ( Do Jun Yeong ),박선희 ( Park Seon Hui ),조규향 ( Jo Gyu Hyang ),박종원 ( Park Jong Won ),윤경우 ( Yun Gyeong U ),조동규 ( Jo Dong Gyu ),이은계 ( Lee Eun Gye ),김인산 ( Kim 대한신장학회 2003 춘계학술대회 초록집 Vol.22 No.1
허혈성 급성신부전에서 TGF-β-induced gene product βig-h3의 변화와 초기 표지자로서의 의의
최민정 ( Min Jeong Choi ),박선희 ( Sun Hee Park ),김찬덕 ( Chan Duck Kim ),김용림 ( Yong Lim Kim ),권태환 ( Tae Hwan Kwon ),김인산 ( In San Kim ),김용진 ( Yong Jin Kim ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.3
Purpose : Acute renal failure remains a potentially devastating clinical problem. This study aimed to examine whether the expression of TGF-β-induced gene product, βig-h3, is altered in ischemiareperfusion (I/R) injury and urinary excretion of βig-h3 is changed in I/R injury. Methods : I/R injury was performed by clamping both renal arteries. Daily urine output, serum creatinine and urinary TGF-β and βig-h3 were measured after I/R injury. Also, the renal expression of βig-h3 by western blotting and immunohistochemistry were investigated. In the second step, urinary βig-h3 was measured at 4, 10, 16, and 24 hours after I/R injury to investigate whether it could be used as an early and sensitive marker for detecting I/R injury. Results : Urinary βig-h3 was significantly elevated at 24 hours and maintained higher than the controls until 2 days after I/R injury. In contrast, western blotting did not reveal any changes of βig-h3 expression. Immunohistochemistry showed that labeling of βig-h3 was seen at the basement membranes of proximal tubule cells mainly located at the medullary ray (S3 segment) in both groups. Following I/injury, the labeling was also seen in the basement membrane of injured or regenerated proximal tubular epithelial cells. Within 24 hours, urinary βig-h3 was significantly increased at 4 hours after I/R injury. Importantly, the urinary appearance of βig-h3 preceded that of N-acetyl-β-D-glucosaminidase. Conclusion : These results suggest that endogenous renal βig-h3 may serve to promote tissue regeneration in I/R injury and urinary βig-h3 could be used as an early and sensitive marker demonstrating I/R injury.
하승우 ( Ha Seung U ),여희진 ( Yeo Hui Jin ),정귀화 ( Jeong Gwi Hwa ),김정국 ( Kim Jeong Gug ),김인산 ( Kim In San ),김보완 ( Kim Bo Wan ) 한국지질동맥경화학회 ( 구 한국지질학회 ) 2002 韓國脂質學會誌 Vol.12 No.1
TGF-β-induced gene-h3 (βig-h3) is an adhesive molecule whose expression is induced by TGF-β. Considering that TGF-β plays an important role in diabetic complications, we hypothesized that βig-h3 may also play a role in the development of diabetic angiopat
흰쥐의 간섬유화 과정에서의 교원질의 다형성 및 양적 변동
조준승,류현모,은선진,김인산 ( Joon Seung Jo,Hyun Mo Ryoo,Sun Jin Eun,In San Kim ) 생화학분자생물학회 1991 BMB Reports Vol.24 No.4
Macromolecular collagen components in rat liver at different stage of fibrosis induced by common bile duct ligation were studied. Animals were killed on the 3rd, 7th, 14th, 21st and 29th day after bile duct ligation and liver specimens and blood samples were obtained. Hepatic collagen was fractionated into neutral salt soluble, acid soluble, pepsin soluble and insoluble fractions, and hydroxyproline content of each fraction was determined. The collagen content, especially in insoluble fraction, was increased as the duration of biliary obstruction increased. Pepsin solubilized collagens were subjected to determination of the collagen types by SDS-polyacrylamide disc gel electrophoresis. The ratio of type I to type III collagen was decreased gradually with progression of fibrosis. These results indicate that an alteration in tissue collagen polymorphism as well as variations in the collagen solubility accompany the fibrotic process, suggesting possible pathogenetic implication.
Collagen Dynamics and Polymorphism in Rat Liver During Fibrogenesis
조준승,류현모,은선진,김인산,Jo, Joon-Seung,Ryoo, Hyun-Mo,Eun, Sun-Jin,Kim, In-San Korean Society for Biochemistry and Molecular Biol 1991 한국생화학회지 Vol.24 No.4
Macromolecular collagen components in rat liver at different stage of fibrosis induced by common bile duct ligation were studied. Animals were killed on the 3rd, 7th, 14th, 21st and 29th day after bile duct ligation and liver specimens and blood samples were obtained. Hepatic collagen was fractionated into neutral salt soluble, acid soluble, pepsin soluble and insoluble fractions, and hydroxyproline content of each fraction was determined. The collagen content, especially in insoluble fraction, was increased as the duration of biliary obstruction increased. Pepsin solubilized collagens were subjected to determination of the collagen types by SDS-polyacrylamide disc gel electrophoresis. The ratio of type I to type III collagen was decreased gradually with progression of fibrosis. These results indicate that an alteration in tissue collagen polymorphism as well as variations in the collagen solubility accompany the fibrotic process, suggesting possible pathogenetic implication. 백서의 총담관을 결찰하여 간섬유화를 유발하고, 그 진행에 따른 간조직내 교원질의 양적 및 질적 변화를 조사하였다. 실험동물의 총담관을 결찰하고 각각 3,7,14,21 그리고 28일째 되는 날에 얻은 간조직과 혈액을 시료로 사용하였다. 간조직내 교원질을 neutral soluble, acid soluble, pepsin soluble 그리고 insoluble fraction으로 분획채취 하였으며, 각 분획의 hydroxyproline 함량으로 교원질을 측정하였다. 담관폐쇄 이후 간기능의 저하가 나타났고, 기간이 길어짐에 따라 간경화의 척도인 간장과 비장의 종대 및 복수의 생성을 관찰하였다. 또한 담관 폐쇄기간이 길수록 간조직의 교원질 함량은 증가하였으며, 특히 insoluble fraction의 증가가 주를 이루었다. Pepsin soluble fraction을 SDS-PAGE한 결과, type I에 대한 type III 교원질의 상대적 비율이 정상조직의 20%에서 4주군에서는 45%까지 증가하였다. 이러한 결과는 섬유화가 진행됨에 따라 교원질의 양적인 변화 뿐 아니라 용해도의 변화 혹은 결합조직을 형성하는 교원질 구성의 변화 등 질적인 변화가 발생함을 보여주고 있으며, 섬유화의 발생기작과 관계가 있을 것으로 볼 수 있다.