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Tight Junctions01:29

Tight Junctions

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Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
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Anchoring Junctions01:03

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Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
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Glycosaminoglycans01:23

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Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
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Hyaluronic...
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Adherens Junctions01:24

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Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
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Overview of Cell-Cell Junctions01:14

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The complex three-dimensional arrangement of cells in any multicellular organism is defined and maintained by interactions of cells with each other and the extracellular matrix. Cell-cell junctions are specialized structures where the multi-protein complexes on one cell interact with the multi-protein complexes on another  cell. These cell junctions are classified  into three main types based on their function — occluding, anchoring, and gap junctions.
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In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
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Hyaluronan cable formation by ocular trabecular meshwork cells.

Ying Ying Sun1, Kate E Keller1

  • 1Casey Eye Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.

Experimental Eye Research
|August 7, 2015
PubMed
Summary

Hyaluronan (HA) cable formation in ocular cells is influenced by various stimuli, but rearranging HA into cables does not affect aqueous humor outflow resistance. The ratio of HA chains produced by different genes is key to cable formation.

Keywords:
Aqueous outflowExtracellular matrixGlaucomaHyaluronanTrabecular meshwork

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Area of Science:

  • Ocular Biology
  • Biochemistry
  • Extracellular Matrix Research

Background:

  • Hyaluronan (HA) in the trabecular meshwork (TM) regulates aqueous humor outflow.
  • HA can form cable-like structures with distinct functional properties.
  • Understanding HA structural changes in TM cells is crucial for ocular health.

Purpose of the Study:

  • To investigate how TM cells alter HA structure in response to stimuli.
  • To determine the impact of HA cable formation on aqueous outflow resistance.
  • To explore the role of gene expression and protein interactions in HA remodeling.

Main Methods:

  • Primary TM cell cultures treated with TNFα, IL-1α, TGFβ2, or mechanical stretch.
  • HA structural configuration assessed via HAbp staining and confocal microscopy.
  • Gene expression (HAS genes) quantified by RT-PCR; HA concentration measured by ELISA.
  • TSG-6 and IαI protein levels analyzed by immunofluorescence and Western immunoblotting.
  • Porcine anterior segments perfused to assess outflow resistance after polyI:C treatment.

Main Results:

  • TNFα, TGFβ2, and mechanical stretch induced HA cable formation; IL-1α did not.
  • HAS gene expression varied temporally and by treatment.
  • HA concentration increased with TNFα, TGFβ2, and IL-1α, but decreased with mechanical stretch.
  • TSG-6 and IαI levels increased with TNFα, TGFβ2, and IL-1α, but decreased with mechanical stretch.
  • PolyI:C treatment did not significantly alter outflow resistance in porcine eyes.
  • Substrate type influenced IαI·TSG-6·HA complex formation.

Conclusions:

  • TM cell responses to ECM remodeling stimuli involve differential HAS gene expression and HA concentration changes.
  • HA cable formation is primarily determined by the ratio of HA chains produced by different HAS genes.
  • Rearranging pericellular HA into cable-like structures does not appear to influence aqueous outflow resistance.