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Int. J. Mol. Sci. 2017, 18(12), 2537; https://doi.org/10.3390/ijms18122537

Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the Fibrosis Process

1
Laboratory of Mathematics and Applications (LMA), DACTIM, UMR CNRS 7348, CHU de Poitiers and University of Poitiers, 86021 Poitiers, France
2
Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien (GHEF), 77100 Meaux, France
3
CHU Amiens Picardie, University of Picardie Jules Verne (UPJV), 80025 Amiens, France
*
Author to whom correspondence should be addressed.
Received: 4 October 2017 / Revised: 10 November 2017 / Accepted: 21 November 2017 / Published: 27 November 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Fibrosis is characterized by fibroblast proliferation and fibroblast differentiation into myofibroblasts, which generate a relaxation-free contraction mechanism associated with excessive collagen synthesis in the extracellular matrix, which promotes irreversible tissue retraction evolving towards fibrosis. From a thermodynamic point of view, the mechanisms leading to fibrosis are irreversible processes that can occur through changing the entropy production rate. The thermodynamic behaviors of metabolic enzymes involved in fibrosis are modified by the dysregulation of both transforming growth factor β (TGF-β) signaling and the canonical WNT/β-catenin pathway, leading to aerobic glycolysis, called the Warburg effect. Molecular signaling pathways leading to fibrosis are considered dissipative structures that exchange energy or matter with their environment far from the thermodynamic equilibrium. The myofibroblastic cells arise from exergonic processes by switching the core metabolism from oxidative phosphorylation to glycolysis, which generates energy and reprograms cellular energy metabolism to induce the process of myofibroblast differentiation. Circadian rhythms are far-from-equilibrium thermodynamic processes. They directly participate in regulating the TGF-β and WNT/β-catenin pathways involved in energetic dysregulation and enabling fibrosis. The present review focusses on the thermodynamic implications of the reprogramming of cellular energy metabolism, leading to fibroblast differentiation into myofibroblasts through the positive interplay between TGF-β and WNT/β-catenin pathways underlying in fibrosis. View Full-Text
Keywords: aerobic glycolysis; canonical WNT/β-catenin pathway; circadian rhythms; fibrosis; TGF-β; Warburg effect aerobic glycolysis; canonical WNT/β-catenin pathway; circadian rhythms; fibrosis; TGF-β; Warburg effect
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Vallée, A.; Lecarpentier, Y.; Vallée, J.-N. Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the Fibrosis Process. Int. J. Mol. Sci. 2017, 18, 2537.

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