Role of Human Primary Renal Fibroblast in TGF-β1-Mediated Fibrosis-Mimicking Devices.

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.

• 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
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 19 (Oct 05 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34639099 (Publication Type: Journal Article)

Chemical References

• TGFB1 protein, human
• Transforming Growth Factor beta1

Topics

• Cells, Cultured
• Endothelium, Vascular (drug effects, metabolism, pathology)
• Fibroblasts (drug effects, metabolism, pathology)
• Fibrosis (chemically induced, metabolism, pathology)
• Humans
• Kidney Tubules, Proximal (drug effects, metabolism, pathology)
• Printing, Three-Dimensional (instrumentation)
• Transforming Growth Factor beta1 (pharmacology)