Fibrosis is a multifactorial process characterized by the excessive accumulation of extracellular matrix (ECM), increased tissue stiffness, and decreased elasticity. To understand how growth factor mediated dysregulation of fibroblasts leads to alterations in the biomechanics of the ECM, we’ve developed a new long term model whereby human fibroblasts form a fibrous 3D ring-shaped tissue whose tensile strength and stiffness steadily increases over three weeks. As the rings compact, cellularity and total DNA decrease, whereas total collagen accumulates. TGF-β1 stimulates collagen accumulation and increases ring biomechanics at day 7, but these increases stall and decline by day 21. When treated with IL-13, a cytokine exclusive to the immune system, there are no significant differences from control. However, when TGF-β1 is combined with IL-13, collagen levels and ring biomechanics increase over the three weeks in culture to levels higher than TGF-β1 alone. Gene expression is differentially regulated by growth factor treatment over the duration in culture and suggests that increased collagen accumulation is not due to upregulation of collagen gene expression. These results suggest that TGF-β1 requires a second signal, such as IL-13, to sustain the long-term pathological increases in collagen accumulation and biomechanics that can compromise the function of fibrotic tissues.
Hopkins, Caitlin Marie,
"TGF-β1 requires IL-13 to sustain collagen accumulation and increasing tissue strength and stiffness"
(2023).
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:dn895gyw/
