Slow interstitial fluid flow activates TGF-β signaling and drives fibrotic responses in human tenon fibroblasts : = Slow interstitial fluid flow activates TGF-[Beta] signaling and drives fibrotic responses in human tenon fibroblasts

Abstract: 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

Object Details

• Alternative title: Slow interstitial fluid flow activates TGF-[Beta] signaling and drives fibrotic responses in human tenon fibroblasts
• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Cells. - 12, 17 (2023) , 2205, ISSN: 2073-4409

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Wiedenmann, Cornelius Jakob ; Gottwald, Charlotte ; Zeqiri, Kosovare ; Frömmichen, Janne ; Bungert, Emma ; Gläser, Moritz ; Ströble, Jeanne ; Lohmüller, Robert ; Reinhard, Thomas ; Lübke, Jan ; Schlunck, Günther

Further information

• DOI: 10.3390/cells12172205
• URN: urn:nbn:de:bsz:25-freidok-2390175
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:58 AM CEST