1.Altered Transendothelial Transport of Hormones as a Contributor to Diabetes.
Nanyoung YOON ; Thanh Q DANG ; Helen CHASIOTIS ; Scott P KELLY ; Gary SWEENEY
Diabetes & Metabolism Journal 2014;38(2):92-99
The vascular endothelium is a dynamic structure responsible for the separation and regulated movement of biological material between circulation and interstitial fluid. Hormones and nutrients can move across the endothelium either via a transcellular or paracellular route. Transcellular endothelial transport is well understood and broadly acknowledged to play an important role in the normal and abnormal physiology of endothelial function. However, less is known about the role of the paracellular route. Although the concept of endothelial dysfunction in diabetes is now widely accepted, we suggest that alterations in paracellular transport should be studied in greater detail and incorporated into this model. In this review we provide an overview of endothelial paracellular permeability and discuss its potential importance in contributing to the development of diabetes and associated complications. Accordingly, we also contend that if better understood, altered endothelial paracellular permeability could be considered as a potential therapeutic target for diabetes.
Adherens Junctions
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Adiponectin
;
Endothelium
;
Endothelium, Vascular
;
Extracellular Fluid
;
Insulin
;
Permeability
;
Physiology
;
Tight Junctions
2.Transmission and Scanning Electron Microscopic Studies on the Sinusoid and the Migration of Erythroid Cell in Rat Fetal Liver.
Yong Wook KIM ; Kyung Yong KIM ; Won Bok LEE ; Heungshik S LEE
Korean Journal of Anatomy 1998;31(2):281-292
For studies on the developmental stages of migrating erythroid cells and the development of sinusoid, transmission and scanning electron microscopic observations were undertaken on rat fetal liver in 13, 15, 17, 19, 21 days of gestation. The results obtained were as follows. 1. The hepatic sinusoidal endothelium were mainly non-fenestrated cell and fenestrated cell with diaphragm before 17 days of gestation, but fenestrated cells without diaphragm began to appear after 17 days of gestation. Two types of fenestrae were observed, free and clustered fenestrae, but both types were not involved in migration of erythroid cells. 2. Endothelial cell was continuous with neighboring cells by intercellular junctions between lateral cytoplasmic processes with zonula adherens, and between perinuclear cytoplasms with macula adherens. 3. After 13 days of gestation, Kupffer cells showed as matured cell morphology of irregular shape with long cytoplasmic processes into hepatic cord and perisinusoidal space. 4. Migrating erythroid cells in rat fetal liver sinusoid were mainly consisted of immature erythroblasts from proerythroblast to acidophilic erythroblast. The migration occurred through the migrating pores formed on the various sites of the endothelial cytoplasm into the hepatic sinusoidal lumen with no relation to the maturation stages of erythroblast and endothelial cell. In summary, the migration of erythroid cells in the sinusoid of rat fetal liver occurred through the invasion and migration pores transiently formed at various sites of endothelial cytoplasm, and migrating erythroid cells were mainly nucleated immature types.
Adherens Junctions
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Animals
;
Cytoplasm
;
Diaphragm
;
Emigration and Immigration
;
Endothelial Cells
;
Endothelium
;
Erythroblasts
;
Erythroid Cells*
;
Intercellular Junctions
;
Kupffer Cells
;
Liver*
;
Pregnancy
;
Rats*
3.The Long-term Effects of Experimental Total Retinectomy.
Jae Heung LEE ; Jong Woo KIM ; Young Bokk HAN
Journal of the Korean Ophthalmological Society 1987;28(2):343-352
Experimental total retinectomy was performed in the pigmented rabbt eyes to investigate its long-term effects on the operated and nonoperated opposite eyes in clinical and histological aspects. Measurement of intraocular pressures, slit lamp biomicroscopy, and indirect ophthalmoscopy were performed before operation and one, two, three and six months after operation. The eyeballs were enucleated six months after operation to make specimens for light and electron microscopy. There was no statistically significant change of intraocular pressure between preoperative and postopzrative measurements during the experimental period. Rubeosis iridis, intraocular hemorrhage and phthisis bulbi were not noticed in the operated and the opposite eyes. Light microscopic examination showed the cangestion of the choroidal vessels. Transmission electron microscopic examination showed apical mounding of the retinal pigment epithelium. Apical processes were short and reduced in number. There were scattered areas of retinal pigment epithelial cdl proliferation. Apical processes of retinal pigment epithelial cells interdigitated with surface processes of the proliferating retinal pigment epithelial cells. There were numerous melanosomes in the cytoplasm of the proliferating retinal pigment epithelial cells. Zonula occludens and zonula adherens between the retinal pigment epithelial cells were well preserved. These results suggest that total retinectomy could preserve the eyeball in the rabbit eyes during the experimental period, total retinectomy, intraocular pressure, choroidal congestion, phthisis bulbi, retinal pigment epithelium
Adherens Junctions
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Choroid
;
Cytoplasm
;
Epithelial Cells
;
Estrogens, Conjugated (USP)
;
Hemorrhage
;
Intraocular Pressure
;
Melanosomes
;
Microscopy, Electron
;
Ophthalmoscopy
;
Retinal Pigment Epithelium
;
Retinaldehyde
;
Tight Junctions
4.Invasion Suppressor Role of E-Cadherin in Epithelial Cancer Cell Lines.
Annals of Dermatology 1997;9(4):263-269
BACKGROUND: The generation of the invasiveness in transfromed cells represents an essential step of tumor progression. The primary cause of the scattering of the cells in invasive carcinoma is a loss of the integrity of the intercellular adherens junction often involving loss of a functional cell-cell adhesion molecule E-cadherin. Therefore, the perturbation of E-cadherin function causes diaggregation of tumor cells and may promote the invasion and metastases. OBJECTIVE: The reduction in E-cadherin activity seems to correlate with the infiltrative ability of tumor cells. The purpose of this study was to compare the E-cadherin expression among different cell lines which were normal to undifferentiated and to check the virtual relationaship between E-cadherin and invasiveness. METHODS: We used 5 cell lines, HaCaT, A431, C3, SiHa and HeLa cell. To check the expression patterns and amounts of E-cadherin in each cell line, immunofluorescence staining, Western blot anlysis and Northern blot analysis were done. An in vitro invasion assay using the collagen gel and MRC-5 fibroblast under the influence of HECD-1 antibody which block the E-cadherin function was done to measure the invasiveness of tumor cells. Collagenase activity in culture supernatants of each cell were analyzed by zymography. RESULTS: Immunofluorescence staining revealed a homogenously well preserved pattern in HaCat, A431, C3 cells. SiHa cells showed patch distribution but HeLa cells did not express the E-cadherin. Western blot analysis and Northern blot results largely corresponded with the immunofluorescence results. The in vitro invasion assay revealed invasion into the collagen matrix of the HeLa cells. When HECD-1 antibody was added to the medium, other cells showed partially disrupted stratification. The collagenolytic activity at 72 kDa sixe was detected in the HeLa cell line only. CONCLUSION: There is an inverse relationship between E-cadherin expression and tumor invasion. Therefore, through their regulation of cell adhesion and motility, cadherin plays a crucial role in the suppression of tumor invasion and metastasis.
Adherens Junctions
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Blotting, Northern
;
Blotting, Western
;
Cadherins*
;
Cell Adhesion
;
Cell Line*
;
Collagen
;
Collagenases
;
Fibroblasts
;
Fluorescent Antibody Technique
;
HeLa Cells
;
Humans
;
In Vitro Techniques
;
Neoplasm Metastasis
5.Luteolin Induces Apoptosis via Mitochondrial Pathway and Inhibits Invasion and Migration of Oral Squamous Cell Carcinoma by Suppressing Epithelial-Mesenchymal Transition Induced Transcription Factors
Bong Soo PARK ; Jong Jin KIL ; Hae Mi KANG ; Su Bin YU ; Dan Bi PARK ; Jin A PARK ; In Ryoung KIM
International Journal of Oral Biology 2018;43(2):69-76
Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy. Numerous therapies have been proposed for its cure. Research is continually being conducted to develop new forms of treatment as current therapies are associated with numerous side-effects. Luteolin, a common dietary flavonoid, has been demonstrated to possess strong anti-cancer activity against various human cancer cell lines. Nevertheless, research into luteolin-based anticancer activity against oral cancer remains scarce. Thus, the objective of this study was to assess the effect of luteolin as an anti-cancer agent. After treatment with luteolin, Ca9-22 and CAL-27 oral cancer cells showed condensed nuclei and enhanced apoptotic rate with evidence of mitochondria-mediated apoptosis. Epithelialmesenchymal transition (EMT) is closely related to tumor migration and invasion. Luteolin suppressed cancer cell invasion and migration in the current study. Elevated expression of E-cadherin, an adherens junction protein, was evident in both cell lines after luteolin treatment. Luteolin also significantly inhibited transcription factors (i.e., N-cadherin, Slug, Snail, Twist, and ZEB-1) that regulated expression of tumor suppressors such as E-cadherin based on Western blot analysis and quantitative PCR. Thus, luteolin could induce mitochondrial apoptosis and inhibit cancer cell invasion and migration by suppressing EMT-induced transcription factors.
Adherens Junctions
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Apoptosis
;
Blotting, Western
;
Cadherins
;
Carcinoma, Squamous Cell
;
Cell Line
;
Epithelial Cells
;
Epithelial-Mesenchymal Transition
;
Gastropoda
;
Humans
;
Luteolin
;
Mouth Neoplasms
;
Polymerase Chain Reaction
;
Snails
;
Transcription Factors
6.Dynamic assembly of intercalated disc during postnatal development in the rat myocardium.
Jian-Ping DOU ; Bo JIAO ; Juan-Juan SHENG ; Zhi-Bin YU
Acta Physiologica Sinica 2014;66(5):569-574
The intercalated disc (ICD) complex of cardiomyocyte consists of fascia adherens, desmosomes and gap junctions which are mainly constructed by their transmembrane proteins: N-cadherin (N-cad), desmoglein-2 (DSG2) and connexin 43 (Cx43), respectively. The aim of this study was to observe the dynamic changes in colocalization of N-cad, DSG2 and Cx43 with each other in the rat left ventricular myocardium at 1, 7, 14, 28 and 90 day(s) after birth (P1, P7, P14, P28 and P90) using immunofluorescent staining. The results showed that, N-cad, DSG2 and Cx43 located all around the plasma membrane at the P1. These proteins accumulated to the long ends of cardiomyocytes, indicating preliminary formation of the ICD at the P7. The localization of three proteins at the ICD increased progressively, but their lateral localization showed an inverse trend from the P14 to P90. However, Cx43 still kept a certain amount of lateral localization in cardiomyocytes even at the P90 as compared with N-cad and DSG2. Quantitative colocalization of proteins was analyzed by the stereological method. Total percentage of colocalization of N-cad with DSG2 was 33.5% at the P1, and increased to 38.6% at the P7, 9.4% in ICD and 29.2% in lateral side. The total percentage of colocalization of N-cad with DSG2 increased to 65.7% at the P90, ICD colocalization increasing to 60.5% and lateral colocalization decreasing to 5.2%. Total percentage of colocalization of N-cad with Cx43 increased from 10.3% at the P1 to 37.1% at the P90, and only ICD colocalization increased, but lateral colocalization kept about 5%. The colocalization pattern of DSG2 with Cx43 was similar to that of N-cad with Cx43. Total percentage of colocalization of N-cad with DSG2 was higher than those of N-cad or DSG2 with Cx43. The above results suggest that the formation of mechanical junctions at the ICD of cardiomyocyte is prior to that of electrochemistry junctions during postnatal development. In other words, cardiomyocyte growth needs a stable mechanical environment at first.
Adherens Junctions
;
metabolism
;
Animals
;
Cadherins
;
metabolism
;
Cell Membrane
;
metabolism
;
Connexin 43
;
metabolism
;
Desmoglein 2
;
metabolism
;
Desmosomes
;
metabolism
;
Gap Junctions
;
metabolism
;
Heart
;
growth & development
;
Heart Ventricles
;
metabolism
;
Myocytes, Cardiac
;
metabolism
;
Rats
7.Effects of Angiotensin II on ZO-1 in Glomerular Epithelial Cells.
Korean Journal of Nephrology 2007;26(5):516-525
PURPOSE: Angiotensin II plays a potent role in renal injury not only by vasoconstrictive effects but also by biochemical effects. We investigated the effect of angiotensin II on ZO-1 (zonular occludens-1), a component of the slit diaphragm domain connecting slit diaphragm structure and actin cytoskeleton, in the glomerular epithelial cells (podocytes) for the glomerular damage. We tried to find that this effect could be prevented by losartan, an angiotensin II type 1 receptor blocker. METHODS: Glomerular epithelial cells were treated with various concentrations of angiotensin II and losartan. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. RESULTS: The intensities of fluorescences and bands of ZO-1 protein were decreased by angiotensin II in a dose-dependent manner by confocal microscopy and Western blot analysis, respectively. ZO-1 also moved from peripheral to inner cytoplasm and lost its linear pattern. These distributional changes of ZO-1 protein by angiotensin II were reversed by losartan in a dose-dependent manner. Angiotensin II reduced the amount and mRNA expresssion of ZO-1 which were also reversed by losartan. CONCLUSION: Angiotensin II decreases the amount of ZO-1 protein and changes its localization through angiotensin II type 1 receptor. These findings suggest that angiotensin II-added condition induces the cytoplasmic translocation and suppresses the production of ZO-1 in podocytes at transcriptional level, and could be prevented by angiotensin receptor antagonists.
Actin Cytoskeleton
;
Adherens Junctions
;
Angiotensin II Type 1 Receptor Blockers
;
Angiotensin II*
;
Angiotensin Receptor Antagonists
;
Angiotensins*
;
Blotting, Western
;
Cytoplasm
;
Diaphragm
;
Epithelial Cells*
;
Losartan
;
Microscopy, Confocal
;
Podocytes
;
Receptor, Angiotensin, Type 1
;
RNA, Messenger
8.Effects of RhoA on the adherens junction of murine ameloblasts.
Liu YANG ; Xiao Yu CHU ; Qi ZHAO
Journal of Peking University(Health Sciences) 2018;50(3):521-526
OBJECTIVE:
To investigate the regulation mechanism of RhoA signaling pathway during the enamel formation by using the EGFP-RhoADominant Negative (EGFP-RhoADN) transgenic mice model, from the aspect of adherens junctions, and to provide a theory basis for mechanism of enamel development defects.
METHODS:
The enamel thickness of mandibular first molars of EGFP-RhoADN transgenic mice and wild type (WT) mice were observed by scanning electronic microscopy at 20 kV, and the enamel thickness of the distal face of the central cusp was measured at 10 locations via analysis by ImageJ (Rasband, 1997-2009). The enamel organs from mandibular first molars from postnatal-4-day (P4) EGFP-RhoADN mice and wild type mice were isolated, and the total RNA and protein were extracted from the epithelium of the enamel organs. The expression level of the adherens junctions components in ameloblasts layer of the postnatal-4-day EGFP-RhoADN transgenic mice and wild type mice mandibular first molars were detected by real-time PCR and Western blot assay.
RESULTS:
The EGFP-RhoADN transgenic mice had decreased enamel thickness in their bilateral mandibular first molars versus those of control group (n=20), and enamel thickness was (84.60±0.20) μm vs. (106.24±0.24) μm, P<0.05. The protein expressions of E-cadherin, α-E-catenin and pan-cadherin in ameloblasts layer of postnatal-4-day EGFP-RhoADN transgenic mice molars were down-regulated, and the protein level of β-catenin in ameloblasts layer of P4 EGFP-RhoADN transgenic mice molars was up-regulated. The mRNA level of E-cadherin in ameloblasts layer of P4 EGFP-RhoADN transgenic mice molars was down-regulated versus that of WT mice, and the gene expression of E-cadherin was 0.93±0.01 vs. 1.00±0.02, P<0.05. The mRNA level of β-catenin in ameloblasts layer of P4 EGFP-RhoADN transgenic mice molars was up-regulated versus that of WT mice, and the gene expression of β-catenin was 1.23±0.03 vs. 1.00±0.05, P<0.05.
CONCLUSION
In the mandibular first molars of EGFP-RhoADN transgenic mice, the enamel formation was disrupted and the adherens junctions of EGFP-RhoADN transgenic mice ameloblasts were implicated during amelogenesis. RhoA signaling pathway may play a critical role in enamel development by altering the adherens junctions in ameloblasts.
Adherens Junctions
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Ameloblasts
;
Amelogenesis
;
Animals
;
Antigens, CD
;
Cadherins/metabolism*
;
Dental Enamel/metabolism*
;
Enamel Organ
;
Humans
;
Mice
;
Mice, Transgenic
;
Molar
;
Signal Transduction
;
alpha Catenin
;
beta Catenin
;
rhoA GTP-Binding Protein/physiology*