The Influence of a Nanopatterned Scaffold that Mimics Abnormal Renal Mesangial Matrix on Mesangial Cell Behavior

• Published in: International journal of molecular sciences 2019-10, Vol.20 (21), p.5349
• Main Authors: Chang, Chia-Jung, Minei, Rin, Sato, Takeshi, Taniguchi, Akiyoshi
• Format: Article
• Language: English
• Subjects: Actin; Actins - metabolism; Animals; Biomarkers; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Collagen; Collagen (type I); Collagen (type IV); Collagen Type I - metabolism; Collagen Type IV - metabolism; Fibronectin; Fibronectins - metabolism; Glomerular Mesangium - cytology; Growth factors; Heparan sulfate; Integrins - metabolism; Kidney diseases; Kidney Diseases - metabolism; Kidney Diseases - pathology; Laminin; Laminin - metabolism; Mesangial cells; Mesangial Cells - cytology; Mesangial Cells - metabolism; Mesangial Cells - pathology; Mesangial Cells - ultrastructure; mesangial matrix; Mesangium; Mice; Molecular modelling; Morphology; Muscles; Nanostructures - chemistry; Nanostructures - toxicity; Nanostructures - ultrastructure; Scanning electron microscopy; Smooth muscle; tio2-based nanopattern; Titanium - chemistry; Titanium dioxide; Topography; Transforming Growth Factor beta - metabolism; Transforming growth factor-b1; type i collagen (col1); type iv collagen (col4)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20215349

The alteration of mesangial matrix (MM) components in mesangium, such as type IV collagen (COL4) and type I collagen (COL1), is commonly found in progressive glomerular disease. Mesangial cells (MCs) responding to altered MM, show critical changes in cell function. This suggests that the diseased MM structure could play an important role in MC behavior. To investigate how MC behavior is influenced by the diseased MM 3D nanostructure, we fabricated the titanium dioxide (TiO )-based nanopatterns that mimic diseased MM nanostructures. Immortalized mouse MCs were used to assess the influence of disease-mimic nanopatterns on cell functions, and were compared with a normal-mimic nanopattern. The results showed that the disease-mimic nanopattern induced disease-like behavior, including increased proliferation, excessive production of abnormal MM components (COL1 and fibronectin) and decreased normal MM components (COL4 and laminin α1). In contrast, the normal-mimic nanopattern actually resulted in cells displaying normal proliferation and the production of normal MM components. In addition, increased expressions of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and integrin α5β1 were detected in cells grown on the disease-mimic nanopattern. These results indicated that the disease-mimic nanopattern induced disease-like cell behavior. These findings will help further establish a disease model that mimics abnormal MM nanostructures and also to elucidate the molecular mechanisms underlying glomerular disease.