ArticlePloS one2017
Engineered extracellular matrices with controlled mechanics modulate renal proximal tubular cell epithelialization.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- Advances in mechanical force-induced adaptive responses and pathological transition of renal tubular epithelial cells.Frontiers in cell and developmental biology · 2026Review
- Article
- Mathematical modelling of mechanotransduction via RhoA signalling pathways.PLoS computational biology · 2025Article
- Sustained alterations in proximal tubule gene expression in primary culture associate with HNF4A loss.Scientific reports · 2024Article
- Mechanisms underlying divergent relationships between CaThe Journal of physiology · 2023Article
- Contribution of mechanical homeostasis to epithelial-mesenchymal transition.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Kidney-on-a-Chip: Mechanical Stimulation and Sensor Integration.Sensors (Basel, Switzerland) · 2022Review
- Mimicking the Natural Basement Membrane for Advanced Tissue Engineering.Biomacromolecules · 2022Review
- Role of extracellular matrix components and structure in new renal modelsFrontiers in physiology · 2022Review
- Renal Biology Driven Macro- and Microscale Design Strategies for Creating an Artificial Proximal Tubule Using Fiber-Based Technologies.ACS biomaterials science & engineering · 2021Review
- A spatial model of YAP/TAZ signaling reveals how stiffness, dimensionality, and shape contribute to emergent outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Silk Film Stiffness Modulates Corneal Epithelial Cell Mechanosignaling.Macromolecular chemistry and physics · 2021Article
- Cell-mediated matrix stiffening accompanies capillary morphogenesis in ultra-soft amorphous hydrogels.Biomaterials · 2020Article
- Article
- Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture.Tissue engineering. Part A · 2019Article
- Sprouting angiogenesis induces significant mechanical heterogeneities and ECM stiffening across length scales in fibrin hydrogels.Biomaterials · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI. PEG diacrylate based hydrogels were generated with orthogonal control of mechanics and cell-substrate interactions. Using this platform, we found that increased substrate stiffness promotes RPTEC spreading and proliferation. RPTECs showed similar degrees of apoptosis and Yes-associated protein (YAP) nuclear localization regardless of stiffness, suggesting these were not key mediators of the effect. However, focal adhesion formation, cytoskeletal organization, focal adhesion kinase (FAK) activation, and extracellular signal-regulated kinase (ERK) activation were all enhanced with increasing substrate stiffness. Inhibition of ERK activation substantially attenuated the effect of stiffness on proliferation. In long-term culture, hydrogel stiffness promoted the formation of more complete epithelial monolayers with tight junctions, cell polarity, and an organized basement membrane. These data suggest that increased stiffness potentially may have beneficial consequences for the renal tubular epithelium during recovery from AKI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.