| Autor: |
Wiedenmann, Cornelius Jakob, Gottwald, Charlotte, Zeqiri, Kosovare, Frömmichen, Janne, Bungert, Emma, Gläser, Moritz, Ströble, Jeanne, Lohmüller, Robert, Reinhard, Thomas, Lübke, Jan, Schlunck, Günther |
| Předmět: |
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| Zdroj: |
Cells (2073-4409); Sep2023, Vol. 12 Issue 17, p2205, 18p |
| Abstrakt: |
Background: Fibrosis limits the success of filtering glaucoma surgery. We employed 2D and 3D in vitro models to assess the effects of fluid flow on human tenon fibroblasts (HTF). Methods: HTF were exposed to continuous or pulsatile fluid flow for 48 or 72 h, at rates expected at the transscleral outflow site after filtering surgery. In the 2D model, the F-actin cytoskeleton and fibronectin 1 (FN1) were visualized by confocal immunofluorescence microscopy. In the 3D model, mRNA and whole cell lysates were extracted to analyze the expression of fibrosis-associated genes by qPCR and Western blot. The effects of a small-molecule inhibitor of the TGF-β receptor ALK5 were studied. Results: Slow, continuous fluid flow induced fibrotic responses in the 2D and 3D models. It elicited changes in cell shape, the F-actin cytoskeleton, the deposition of FN1 and activated the intracellular TGF-β signaling pathway to induce expression of fibrosis-related genes, such as CTGF, FN1 and COL1A1. ALK5-inhibition reduced this effect. Intermittent fluid flow also induced fibrotic changes, which decreased with increasing pause duration. Conclusions: Slow interstitial fluid flow is sufficient to induce fibrosis, could underlie the intractable nature of fibrosis following filtering glaucoma surgery and might be a target for antifibrotic therapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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