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Role of Human Primary Renal Fibroblast in TGF-beta 1-Mediated Fibrosis-Mimicking Devices : Role of human primary renal fibroblast in tgf-β1-mediated fibrosis-mimicking devices
Cited 4 time in
Web of Science
Cited 6 time in Scopus
- Authors
- Issue Date
- 2021-10
- Citation
- International Journal of Molecular Sciences, Vol.22 No.19, p. 10758
- Abstract
- Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-beta (TGF-beta) and TGF-beta inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-beta 1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-beta-treated group and TGF-beta-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-beta-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-beta 1, TGF-beta 2, and TGF-beta 3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.
- ISSN
- 1661-6596
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