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Ulrich Welge-Lüßen, Chr. Albrecht May, Elke Lütjen-Drecoll; Induction of Tissue Transglutaminase in the Trabecular Meshwork by TGF-β1 and TGF-β2. Invest. Ophthalmol. Vis. Sci. 2000;41(8):2229-2238.
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purpose. To study whether human trabecular meshwork (HTM) cells are capable of
expressing and secreting tissue transglutaminase (tTgase), an enzyme
cross-linking extracellular matrix (ECM) proteins, and whether tTgase
and synthesis of cross-linked fibronectin are increased after treatment
of HTM cells with transforming growth factor (TGF)-β1 or -β2.
methods. Anterior segments of six normal human eyes were stained with antibodies
to tTgase. Tissues from three eyes were analyzed for tTgase using
Western blot analysis. Monolayer cultures of HTM cells from eyes of
five human donors were treated with 1.0 ng/ml TGF-β1, -β2, or
5 × 10−7 M dexamethasone (DEX) for 12 to 96 hours.
Induction of tTgase was investigated by Western and Northern blot
analysis. External tTgase activity was measured by the ability to form
polymerized fibronectin and the incorporation of biotinylated
cadaverine into fibronectin.
results. Labeling for tTgase was observed throughout the entire HTM. Cultured
HTM cells expressed tTgase intra- and extracellularly. Treatment of
cultured HTM cells with TGF-β1 and -β2 increased the tTgase mRNA
and protein levels, whereas DEX had no effect. TGF-β–treated HTM
cells showed a significant increase in polymerized and unpolymerized
fibronectin. Incorporation of biotinylated cadaverine was markedly
increased when HTM cells were treated with TGF-β for 24 hours before
conclusions. The enzyme tTgase is expressed in the HTM and is inducible by TGF-β1
or -β2 in cultured HTM cells. Extracellular tTgase is able to
polymerize fibronectin. Increased levels of TGF-β2 in the aqueous
humor may lead to an increase of tTgase expression and activity in the
HTM, causing an increase of irreversibly cross-linked ECM proteins.
This mechanism might play a role for the increased outflow resistance
seen in glaucomatous eyes.
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