Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms using Computational Systems Biology Approaches

Version 1 : Received: 31 October 2020 / Approved: 2 November 2020 / Online: 2 November 2020 (19:28:02 CET)

How to cite: Aghakhani, S.; Zerrouk, N.; Niarakis, A. Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms using Computational Systems Biology Approaches. Preprints 2020, 2020110069 (doi: 10.20944/preprints202011.0069.v1). Aghakhani, S.; Zerrouk, N.; Niarakis, A. Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms using Computational Systems Biology Approaches. Preprints 2020, 2020110069 (doi: 10.20944/preprints202011.0069.v1).

Abstract

Fibroblasts, the most abundant cells in the connective tissue, are key modulators of the extracellular matrix (ECM) composition. These spindle-shaped cells are capable of synthesizing various extracellular matrix proteins and collagen. They also provide the structural framework (stroma) for tissues and play a pivotal role in the wound healing process. While they are maintainers of the ECM turnover and regulate several physiological processes, they can also undergo transformations responding to certain stimuli and display aggressive phenotypes that contribute to disease pathophysiology. In this review, we focus on the metabolic pathways of glucose and highlight metabolic reprogramming as a critical event that contributes to the transition of fibroblasts from quiescent to activated and aggressive cells. We also cover the emerging evidence that allows us to draw parallels between fibroblasts in autoimmune disorders and more specifically in rheumatoid arthritis and cancer. We link the metabolic changes of fibroblasts to the toxic environment created by the disease condition and discuss how targeting of metabolic reprogramming could be employed in the treatment of such diseases. Lastly, we discuss Systems Biology approaches, and more specifically, computational modelling, as a means to elucidate pathogenetic mechanisms and accelerate the identification of novel therapeutic targets.

Subject Areas

Fibroblasts; Rheumatoid Arthritis; Cancer; Metabolic Reprogramming; Glycolytic Switch; Systems Biology; Computational Modelling

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.