scholarly journals RhoA‐dependent tight junction regulation is associated with dysregulated Akt and ERK signaling and increased claudin‐2 expression

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Markus Gluth ◽  
Ulrich‐Frank Pape ◽  
Franz Theuring ◽  
Andreas Fischer
Keyword(s):  
Tight Junction ◽  
Erk Signaling ◽  
Tight Junction Regulation

Tight Junction Regulation by Morphine and HIV-1 Tat Modulates Blood–Brain Barrier Permeability

2008 ◽  
Vol 28 (5) ◽  
pp. 528-541 ◽  
Author(s):  
Supriya D. Mahajan ◽  
Ravikumar Aalinkeel ◽  
Donald E. Sykes ◽  
Jessica L. Reynolds ◽  
B. Bindukumar ◽  
...  
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Tight Junction Regulation ◽  
Hiv 1

Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation

1997 ◽  
Vol 273 (4) ◽  
pp. C1378-C1385 ◽  
Author(s):  
Jerrold R. Turner ◽  
Brian K. Rill ◽  
Susan L. Carlson ◽  
Denise Carnes ◽  
Rachel Kerner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junctions ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitors ◽  
Tight Junction Regulation ◽  
Tight Junction Permeability ◽  
Mlc Phosphorylation

Tight junctions serve as the rate-limiting barrier to passive movement of hydrophilic solutes across intestinal epithelia. After activation of Na+-glucose cotransport, the permeability of intestinal tight junctions is increased. Because previous analyses of this physiological tight junction regulation have been restricted to intact mucosae, dissection of the mechanisms underlying this process has been limited. To characterize this process, we have developed a reductionist model consisting of Caco-2 intestinal epithelial cells transfected with the intestinal Na+-glucose cotransporter, SGLT1. Monolayers of SGLT1 transfectants demonstrate physiological Na+-glucose cotransport. Activation of SGLT1 results in a 22 ± 5% fall in transepithelial resistance (TER) ( P< 0.001). Similarly, inactivation of SGLT1 by addition of phloridzin increases TER by 24 ± 2% ( P < 0.001). The increased tight junction permeability is size selective, with increased flux of small nutrient-sized molecules, e.g., mannitol, but not of larger molecules, e.g., inulin. SGLT1-dependent increases in tight junction permeability are inhibited by myosin light-chain kinase inhibitors (20 μM ML-7 or 40 μM ML-9), suggesting that myosin regulatory light-chain (MLC) phosphorylation is involved in tight junction regulation. Analysis of MLC phosphorylation showed a 2.08-fold increase after activation of SGLT1 ( P< 0.01), which was inhibited by ML-9 ( P < 0.01). Thus monolayers incubated with glucose and myosin light-chain kinase inhibitors are comparable to monolayers incubated with phloridzin. ML-9 also inhibits SGLT1-mediated tight junction regulation in small intestinal mucosa ( P < 0.01). These data demonstrate that epithelial cells are the mediators of physiological tight junction regulation subsequent to SGLT1 activation. The intimate relationship between tight junction regulation and MLC phosphorylation suggests that a critical step in regulation of epithelial tight junction permeability may be myosin ATPase-mediated contraction of the perijunctional actomyosin ring and subsequent physical tension on the tight junction.

scholarly journals Apelin-13 Is an Early Promoter of Cytoskeleton and Tight Junction in Diabetic Macular Edema via PI-3K/Akt and MAPK/Erk Signaling Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Yang Li ◽  
Yu-jing Bai ◽  
Yan-rong Jiang ◽  
Wen-zhen Yu ◽  
Xuan Shi ◽  
...  
Keyword(s):  
Tight Junction ◽  
Macular Edema ◽  
Signaling Pathways ◽  
Vascular Permeability ◽  
Diabetic Macular Edema ◽  
High Glucose ◽  
Vision Loss ◽  
Erk Signaling ◽  
Early Event ◽  
Early Promoter

Diabetic macular edema is major cause of vision loss associated with diabetic retinopathy. Breakdown of blood-retinal barrier, especially inner BRB, is an early event in pathogenesis of DR. Apelin, an endogenous ligand of APJ, mediates angiogenesis and is involved in the development of DR. The present study aimed to investigate effects and mechanism of apelin-13 in vascular permeability during DME. We verified apelin-13 was upregulated in DME patients’ vitreous. High glucose incubation led to a progressive increase of apelin-13, APJ, cytoskeleton, and tight junction proteins, including VE-Cadherin, FAK, Src, ZO-1, and occludin. Apelin-13 promoted HRMEC proliferation and migration and phosphorylation of both cytoskeleton and tight junction under both normal and high glucose conditions. Besides, apelin-13 activated PI-3K/Akt and MAPK/Erk signaling pathways, including PLCγ1, p38, Akt, and Erk both in HRMEC and in C57BL/6 mice. Meanwhile, F13A performed opposite effects compared with apelin-13. In in vivo study, apelin-13 was also upregulated in retina of db/db mice. Taken together, apelin-13 increased biologic activity of HRMEC, as well as expression of both cytoskeleton and tight junction in DME via PI-3K/Akt and MAPK/Erk signaling pathways. Apelin-13 as an early promoter of vascular permeability may offer a new perspective strategy in early treatment of DR.

Transepithelial resistance can be regulated by the intestinal brush-border Na+/H+ exchanger NHE3

2000 ◽  
Vol 279 (6) ◽  
pp. C1918-C1924 ◽  
Author(s):  
Jerrold R. Turner ◽  
Eric D. Black ◽  
Jeff Ward ◽  
Chung-Ming Tse ◽  
Frederick A. Uchwat ◽  
...  
Keyword(s):  
Tight Junction ◽  
Myosin Ii ◽  
Transepithelial Resistance ◽  
Cell Swelling ◽  
Intestinal Brush Border ◽  
Tight Junction Regulation ◽  
Cytoplasmic Acidification ◽  
Tight Junction Permeability ◽  
Dimethyl Amiloride ◽  
Mlc Phosphorylation

Initiation of intestinal Na+-glucose cotransport results in transient cell swelling and sustained increases in tight junction permeability. Since Na+/H+ exchange has been implicated in volume regulation after physiological cell swelling, we hypothesized that Na+/H+ exchange might also be required for Na+-glucose cotransport-dependent tight junction regulation. In Caco-2 monolayers with active Na+-glucose cotransport, inhibition of Na+/H+ exchange with 200 μM 5-( N, N-dimethyl)- amiloride induced 36 ± 2% increases in transepithelial resistance (TER). Evaluation using multiple Na+/H+ exchange inhibitors showed that inhibition of the Na+/H+ exchanger 3 (NHE3) isoform was most closely related to TER increases. TER increases due to NHE3 inhibition were related to cytoplasmic acidification because cytoplasmic alkalinization with 5 mM NH4Cl prevented both cytoplasmic acidification and TER increases. However, NHE3 inhibition did not affect TER when Na+-glucose cotransport was inhibited. Myosin II regulatory light chain (MLC) phosphorylation decreased up to 43 ± 5% after inhibition of Na+/H+ exchange, similar to previous studies that associate decreased MLC phosphorylation with increased TER after inhibition of Na+-glucose cotransport. However, NHE3 inhibitors did not diminish Na+-glucose cotransport. These data demonstrate that inhibition of NHE3 results in decreased MLC phosphorylation and increased TER and suggest that NHE3 may participate in the signaling pathway of Na+-glucose cotransport-dependent tight junction regulation.

Tight junction regulation through vesicle trafficking: bringing cells together

2014 ◽  
Vol 42 (1) ◽  
pp. 195-200 ◽  
Author(s):  
Sarah J. Fletcher ◽  
Joshua Z. Rappoport
Keyword(s):  
Steady State ◽  
Tight Junction ◽  
Tight Junctions ◽  
Vesicle Trafficking ◽  
Present Review ◽  
Physiological Processes ◽  
Endosomal Recycling ◽  
Tight Junction Regulation ◽  
Epithelial Layers

Epithelial layers are integral for many physiological processes and are maintained by intercellular adhesive structures. During disease, these structures can disassemble, leading to breakdown of epithelia. TJs (tight junctions) are one type of intercellular adhesion. Loss of TJs has been linked to the pathogenesis of many diseases. The present review focuses on the role of vesicle trafficking in regulation of TJs, in particular trafficking of the TJ protein occludin. We examine how endocytosis and endosomal recycling modulate occludin localization under steady-state conditions and during stimulated TJ disassembly.

ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation

1993 ◽  
Vol 264 (5) ◽  
pp. C1096-C1101 ◽  
Author(s):  
J. L. Madara ◽  
S. Carlson ◽  
J. M. Anderson
Keyword(s):  
Spatial Distribution ◽  
Tight Junction ◽  
Tight Junctions ◽  
Plasma Membranes ◽  
Freeze Fracture ◽  
Cell Junctions ◽  
Absorptive Cell ◽  
Physiological Regulation ◽  
Functional Relationships ◽  
Tight Junction Regulation

Tight junctions restrict diffusion of hydrophilic solutes through the paracellular pathways of columnar epithelia. It is now apparent that the barrier function of tight junctions is physiologically regulated. Current models of the tight junction envisage junctional subunits consisting of extracellular "kisses" between plasma membranes of adjacent cells, intramembrane components represented by freeze-fracture fibrils, and cytoplasmic elements of the cytoskeleton. Insights into functional relationships between these various components of tight junctions should be provided by mapping component interrelationships in states of altered junctional permeability. Here we define the spatial distribution of ZO-1 during a state of physiological regulation of intestinal absorptive cell tight junctions. Enhanced permeation of absorptive cell junctions in response to activation of apical membrane Na(+)-solute cotransporters does not lead to redistribution of the ZO-1 pool, as judged from quantitative ultrastructural immunolocalization studies employing two different ZO-1 antibodies. Surprisingly, ZO-1, which normally localizes under junctional kisses/fibrils, focally persists at sites where junctional kisses/fibrils are cleared. These findings suggest that 1) spatial redistribution of ZO-1 does not contribute to physiological regulation of junctions elicited by activation of Na(+)-solute cotransport and 2) ZO-1 and junctional fibrils may spatially dissociate during such regulated states.

Role of flavonoids in intestinal tight junction regulation

2011 ◽  
Vol 22 (5) ◽  
pp. 401-408 ◽  
Author(s):  
Takuya Suzuki ◽  
Hiroshi Hara
Keyword(s):  
Tight Junction ◽  
Tight Junction Regulation
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