Role of Human Primary Renal Fibroblast in TGF-β1-Mediated Fibrosis-Mimicking Devices |
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Authors: | Seong-Hye Hwang Yun-Mi Lee Yunyeong Choi Hyung Eun Son Ji Young Ryu Ki Young Na Ho Jun Chin Noo Li Jeon Sejoong Kim |
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Affiliation: | 1.Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Korea; (S.-H.H.); (Y.-M.L.); (Y.C.); (H.E.S.); (J.Y.R.); (K.Y.N.); (H.J.C.);2.Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;3.Program for Bioengineering, School of Engineering, Seoul National University, Seoul 08826, Korea |
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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-β (TGF-β) and TGF-β inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-β1 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-β-treated group and TGF-β-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-β-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-β1, TGF-β2, and TGF-β3 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. |
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Keywords: | renal fibroblast fibrosis TGF-β 1 |
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