Establishment of a Nanopatterned Renal Disease Model by Mimicking the Physical and Chemical Cues of a Diseased Mesangial Cell Microenvironment

Chia Jung Chang, Akiyoshi Taniguchi

Research output: Contribution to journalArticlepeer-review

Abstract

Modulation of mesangial cell (MC) response by in vitro disease models offers therapeutic strategies for the treatment of several glomerular diseases. However, traditional cell culture models lack the nanostructured extracellular matrix (ECM), which has unique physical and chemical properties, so they poorly reflect the complexities of the native microenvironment. Therefore, a cell disease model with ECM nanostructures is required to better mimic the in vivo diseased nanoenvironment. To establish a renal disease model, we used a titanium dioxide-based disease-mimic nanopattern as the physical cues and transforming growth factor-beta 1 (TGF-β1) as a chemical cue. The effects of this renal disease model on proliferation and mesangial matrix (MM) component changes in the SV40MES13 (MES13) mouse mesangial cell line were evaluated. Our results showed that both the presence of the disease-mimic nanopattern and TGF-β1 intensified proliferation and resulted in increased type I collagen and fibronectin and decreased type IV collagen expressions in MES13 cells. These effects could be involved in increased TGF-β type I receptor expression in MES13 cells. The intracellular reactive oxygen species (ROS) level as a biomarker of this renal disease model indicated that the cells were in a diseased state. A small molecule A83-01 and known drug dexamethasone markedly attenuated the intracellular ROS production in MES13 that was induced by the disease-mimic nanopattern and TGF-β1. These results highlight the significant effects of physical and chemical cues in facilitating disease-like behavior in MES13 cells, providing an important theoretical basis for developing a drug screening platform for glomerular diseases.

Original languageEnglish
JournalACS Applied Bio Materials
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • ECM
  • intracellular ROS
  • mesangial cells
  • nanopattern
  • proliferation
  • TGF-β1

ASJC Scopus subject areas

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

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