Towards a unified approach in the modeling of fibrosis: A review with research perspectives

Amar, Martine Ben; Bianca, Carlo

doi:10.1016/j.plrev.2016.03.005

Cited by 50 publications

(26 citation statements)

References 241 publications

(229 reference statements)

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“…The development of fibrosis presents a great challenge to researchers202122. The control of fibrosis remains elusive, although some progress has been made232425.…”

Section: Discussionmentioning

confidence: 99%

Involvement of eIF6 in external mechanical stretch–mediated murine dermal fibroblast function via TGF-β1 pathway

Qin

Tan

Daele

et al. 2016

Sci Rep

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External mechanical loading on a wound commonly increases fibrosis. Transforming growth factor-β1 (TGF-β1) has been implicated in fibrosis in various models, including the mechanical force model. However, the underlying mechanism is unclear. Our previous experiments suggested that eukaryotic initiation factor 6 (eIF6) acted as a regulator of TGF-β1 expression, and negatively impact on collagen synthesis. Our current results showed that external mechanical stretching significantly increased COL1A1, TGF-β1 and eIF6 expression as well as dermal fibroblasts proliferation, both in vitro and in vivo. eIF6 –deficient (eIF6+/−) cells exhibited significantly higher levels of COL1A1, and these levels increased further with external mechanical stretching, suggesting that mechanical stretching plays a synergistic role in promoting COL1A1 expression in eIF6+/− cells. Inhibition of TGFβR I/II by LY2109761 decreased COL1A1 protein expression in eIF6+/− dermal fibroblasts in a cell stretching model, and attenuated granulation tissue formation in partial thickness wounds of eIF6+/− mice. These data suggest that mechanical stretching has a synergistic role in the expression of COL1A1 in eIF6+/− cells, and is mediated by activation of TGFβRI/II. Taken together, our results indicate that eIF6 may be involved in external mechanical force-mediated murine dermal fibroblast function at least partly through the TGF-β1 pathway.

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“…The development of fibrosis presents a great challenge to researchers202122. The control of fibrosis remains elusive, although some progress has been made232425.…”

Section: Discussionmentioning

confidence: 99%

Involvement of eIF6 in external mechanical stretch–mediated murine dermal fibroblast function via TGF-β1 pathway

Qin

Tan

Daele

et al. 2016

Sci Rep

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“…As discussed in the review paper [1], ODE-based models are employed for studying the time evolution of the density of the cell populations of the system under consideration; PDE-based models deal with the evolution of systems with an internal structure or a space structure; kinetic theory models are concerned with the modeling of interactions among the entities; continuum mechanics approach is based on the fluid-assumption of the system. Each framework is suitable for the modeling of the complex system depending on what is needed to model.…”

Section: Complexity and Scale Of Representationmentioning

confidence: 99%

“…The commentary articles by Aty [2] and Pappalardo et al [13] focus on the applicability of the agent-based model (ABM) for the analysis of fibrosis diseases. The authors stress the capability of the ABM to be able to link the mesoscopic scale and the macroscopic scale and also mimic features at the molecular level, such as the presence of cellular receptors and receptor recognition mechanisms, see [24,25].…”

Section: Bioinformatics Powers Towards a Multiscale Modelmentioning

confidence: 99%

“…Indeed their critical analysis have allowed to improve the review paper [1]. The raised issues have suggested a further analysis and bibliography investigation that have made the tools of the review paper [1] more comprehensive and applicable.…”

Section: Concluding Remarkmentioning

confidence: 99%

“…Moreover a close examination about the raised open problems is considered. Finally the study of the transport properties in fibrosis is also discussed, a very interesting topic that has been mentioned in the review [1].…”

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confidence: 99%

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Multiscale modeling of fibrosis – What's next? Reply to Comments on “Towards a unified approach in the modeling of fibrosis: A review with research perspective” by Martine Ben Amar and Carlo Bianca

Amar

Bianca

2016

Physics of Life Reviews

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Mathematical models of cystic fibrosis as a systemic disease

Olivença

Davis

Kumbale

et al. 2023

WIREs Mechanisms of Disease

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Cystic fibrosis (CF) is widely known as a disease of the lung, even though it is in truth a systemic disease, whose symptoms typically manifest in gastrointestinal dysfunction first. CF ultimately impairs not only the pancreas and intestine but also the lungs, gonads, liver, kidneys, bones, and the cardiovascular system. It is caused by one of several mutations in the gene of the epithelial ion channel protein CFTR. Intense research and improved antimicrobial treatments during the past eight decades have steadily increased the predicted life expectancy of a person with CF (pwCF) from a few weeks to over 50 years. Moreover, several drugs ameliorating the sequelae of the disease have become available in recent years, and notable treatments of the root cause of the disease have recently generated substantial improvements in health for some but not all pwCF. Yet, numerous fundamental questions remain unanswered. Complicating CF, for instance in the lung, is the fact that the associated insufficient chloride secretion typically perturbs the electrochemical balance across epithelia and, in the airways, leads to the accumulation of thick, viscous mucus and mucus plaques that cannot be cleared effectively and provide a rich breeding ground for a spectrum of bacterial and fungal communities. The subsequent infections often become chronic and respond poorly to antibiotic treatments, with outcomes sometimes only weakly correlated with the drug susceptibility of the target pathogen. Furthermore, in contrast to rapidly resolved acute infections with a single target pathogen, chronic infections commonly involve multi‐species bacterial communities, called “infection microbiomes,” that develop their own ecological and evolutionary dynamics. It is presently impossible to devise mathematical models of CF in its entirety, but it is feasible to design models for many of the distinct drivers of the disease. Building upon these growing yet isolated modeling efforts, we discuss in the following the feasibility of a multi‐scale modeling framework, known as template‐and‐anchor modeling, that allows the gradual integration of refined sub‐models with different granularity. The article first reviews the most important biomedical aspects of CF and subsequently describes mathematical modeling approaches that already exist or have the potential to deepen our understanding of the multitude aspects of the disease and their interrelationships. The conceptual ideas behind the approaches proposed here do not only pertain to CF but are translatable to other systemic diseases.This article is categorized under: Congenital Diseases > Computational Models

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Towards a unified approach in the modeling of fibrosis: A review with research perspectives

Cited by 50 publications

References 241 publications

Involvement of eIF6 in external mechanical stretch–mediated murine dermal fibroblast function via TGF-β1 pathway

Involvement of eIF6 in external mechanical stretch–mediated murine dermal fibroblast function via TGF-β1 pathway

Multiscale modeling of fibrosis – What's next? Reply to Comments on “Towards a unified approach in the modeling of fibrosis: A review with research perspective” by Martine Ben Amar and Carlo Bianca

Mathematical models of cystic fibrosis as a systemic disease

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