Tight junctions (TJ) are named according to their classical function to seal the cleft between epithelial and endothelial cells against unwanted passage of solutes and water. The main protein families of the TJ are claudins, TJ-associated MARVEL proteins (TAMP, including occludin and tricellulin), junctional adhesion molecules (JAM), and angulins, most of which are connected to the cytoskeleton via adapters such as zonula occludens (ZO) proteins. TJ proteins do not only form barriers but, in contrast, some constitute paracellular ion or water channels. The first molecular structures of claudins and models of TJ channel pores are published. This entry collection aims to provide further insight into the complex machinery of the development and control of tissue formation and cell differentiation.

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Topic Review
Protein One-Dimensional Sliding
One-dimensional (1D) sliding of DNA-binding proteins has been observed by numerous kinetic studies. It appears that many of these sliding events play important roles in a wide range of biological processes. However, one challenge is to determine the physiological relevance of these motions in the context of the protein’s biological function. Here, we discuss methods of measuring protein 1D sliding by highlighting the single-molecule approaches that are capable of visualizing particle movement in real time. We also present recent fifindings that show how protein sliding contributes to function. 
  • 102
  • 12 Nov 2021
Topic Review
Association between Membrane Proteins and Disease
Cell membranes, including membrane carrier proteins, membrane channel proteins and ATP drive pumps, are the main transporters. Membrane transporters have wide, but specific tissue distributions. They can impact on multiple endogenous and xenobiotic processes. Transport proteins constitute approximately 10% of most proteomes and play vital roles in the translocation of solutes across the membranes of all organisms. The receptor proteins on the cell membrane are also important structures involved in substrate transport and signal communication. The obstacles of cell transport-related proteins directly lead to the lack or excess of certain substances in cells.
  • 107
  • 04 Nov 2021
Topic Review
Myotendinous Junctions
The myotendinous junction (MTJ) is the muscle-tendon interface and constitutes an integrated mechanical unit to force transmission. Joint immobilization promotes muscle atrophy via disuse, while physical exercise can be used as an adaptative stimulus. In this study, we aimed to investigate the components of the MTJ and their adaptations and the associated elements triggered with aquatic training after joint immobilization. Forty-four male Wistar rats were divided into sedentary (SD), aquatic training (AT), immobilization (IM), and immobilization/aquatic training (IMAT) groups. The samples were processed to measure fiber area, nuclear fractal dimension, MTJ nuclear density, identification of telocytes, sarcomeres, and MTJ perimeter length. In the AT group, the maintenance of ultrastructure and elements in the MTJ region were observed; the IM group presented muscle atrophy effects with reduced MTJ perimeter; the IMAT group demonstrated that aquatic training after joint immobilization promotes benefits in the muscle fiber area and fractal dimension, in the MTJ region shows longer sarcomeres and MTJ perimeter. We identified the presence of telocytes in the MTJ region in all experimental groups. We concluded that aquatic training is an effective rehabilitation method after joint immobilization due to reduced muscle atrophy and regeneration effects on MTJ in rats.
  • 200
  • 20 Jul 2021
Topic Review
Intestinal Permeability and Liver Cirrhosis
An alteration of gut microbiota and their products, particularly endotoxins may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, the so-called “leaky gut.” Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases. The decreased diversity of gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of posttransplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor–alpha, interleukin (IL)–6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is also a major receptor activated by the binding of endotoxins in hepatic stellate cells, which play a crucial role in liver fibrogenesis that could develop into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression.
  • 98
  • 13 Jul 2021
Topic Review
Escherichia coli-Caused Blood–Brain Barrier Disruption
Brain microvascular endothelial cells (BMECs) constitute the structural and functional basis for the blood–brain barrier (BBB) and play essential roles in bacterial meningitis. Electrical cell-substrate impedance sensing (ECIS) measurement and Western blot assay demonstrated lncRSPH9-4 overexpression in hBMECs mediated the BBB integrity disruption.
  • 128
  • 18 Jun 2021
Topic Review
Leptin Cellular Signaling in Brain
The triad of obesity, metabolic syndrome (MetS), Type 2 diabetes mellitus (T2DM) and advancing age are currently global societal problems that are expected to grow over the coming decades. This triad is associated with multiple end-organ complications of diabetic vasculopathy (maco-microvessel disease), neuropathy, retinopathy, nephropathy, cardiomyopathy, cognopathy encephalopathy and/or late-onset Alzheimer’s disease. 
  • 170
  • 01 Jun 2021
Topic Review
CD146 (MCAM)
CD146 is a cell adhesion molecule expressed on all the vascular tree and belongs to the immunoglobulin superfamily. Two isoforms of CD146 exists, a long isoform expressed at the cell junction and a short isoform located at the apical membrane of the cells. CD146 appears to be critical in regulating vascular permeability, cell-cell cohesion, leukocyte transmigration, and angiogenesis. As a consequence, CD146 is involved in the pathogenesis of various diseases including autoimmune diseases and cancers. Also, CD146 exists in a soluble form generated via the action of matrix metalloproteinases and referred to as soluble CD146 (sCD146). The concentration of sCD146 is quantifiable in the sera and cerebrospinal fluid of healthy individuals. Indeed, any variation in its physiological concentration is associated with certain diseases making it an excellent biomarker for diagnostic purposes.  
  • 137
  • 27 Apr 2021
Topic Review
Auraptene enhances Blood brain barrier
The blood-brain barrier (BBB) is a selectively permeable barrier that divides the central nervous system (CNS) from the peripheral circulation, preventing infectious substances and immune cells from entering the CNS.
  • 162
  • 24 Mar 2021
Topic Review
Osteoarthritis (OA) is a most common type of arthritis occur in the aged population. It affects any joint in the body and degenerates the articular cartilage and subchondral bone. Despite the pathophysiology of OA is different, still cartilage resorption is a symbol of osteoarthritis. Matrix metalloproteinases (MMPs) are important proteolytic enzymes that degrade extra-cellular matrix proteins (ECM) in the body. MMPs contribute to the turnover of cartilage and its break down; their levels have increased in the joint tissues of OA patients. Application of chondroprotective drugs neutralize the activities of MMPs. Natural products derived from herbs and plants developed as traditional medicine have paid much attention due to their potential biological effects. Therapeutic value of natural products in OA has increased reputation by presenting clinical impact with insignificant side effects. Several MMPs inhibitor have been used as therapeutic drugs for long time. Recently, different types of compounds have been reviewed for their biological activities. In this review, we summarize numerous natural products for the development as MMPs inhibitors in arthritic diseases and describe the major signaling targets that involved for the treatments of these destructive joint diseases.
  • 290
  • 05 Nov 2020
Topic Review
Sphingosine 1-phosphate
The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one of the most effective EC barrier-stabilizing signaling molecules. Stabilization is mainly transduced via the S1P receptor type 1 (S1PR1). Here, we demonstrate that S1P was autonomously produced by ECs. S1P secretion was significantly higher in primary human umbilical vein endothelial cells (HUVEC) compared to the endothelial cell line EA.hy926. Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab. HUVEC and EA.hy926 differed in the expression of the S1P-transporter Spns2, which allowed HUVEC, but not EA.hy926, to secrete S1P into the extracellular space. Spns2 deficient mice showed increased serum albumin leakage in bronchoalveolar lavage fluid (BALF). Lung ECs isolated from Spns2 deficient mice revealed increased leakage of fluorescein isothiocyanate (FITC) labeled dextran and decreased resistance in electric cell-substrate impedance sensing (ECIS) measurements. Spns2 was down-regulated in HUVEC after stimulation with pro-inflammatory cytokines and lipopolysaccharides (LPS), which contributed to destabilization of the EC barrier. Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2.
  • 321
  • 30 Oct 2020
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