Crosstalk of metabolic and epigenetic pathways in systemic sclerosis (SSc)

Concept

Targeting metabolic pathways in systemic sclerosis (SSc) could represents a promising new treatment strategy in SSc.

Facts and figures

Project lead
B Burja
University Medical Centre Ljubljana
blaz.burja@gmail.com
FOREUM research grant: €150,000
2018–2021

Meet the team

B Burja
University Medical Centre Ljubljana
Prof Dr. M Tomšič
University Medical Centre Ljubljana
K Lakota
University Medical Centre Ljubljana
Prof. Dr. O Distler
University of Zurich
M Frank-Bertoncelj
University of Zurich

Objectives

The aim is to explore dysregulation of metabolic pathways in SSc and determine, whether metabolic substrates, such as aKG, influence the pro-fibrotic activities of SSc fibroblasts. Targeting metabolic pathways might halt fibrosis in SSc with direct implications for drug discovery in SSc

Interim results

The in vitro analyses showed that dm-aKG can efficiently inhibit profibrotic and proinflammatory responses of skin fibroblasts by interfering with the TGFβ-induced myofibroblast differentiation/function, indicating its strong ability to halt fibrotic activation of dermal fibroblasts.

Publications

EULAR Abstracts

2020

  • SAT0292: Integrative transcriptomic and functional analysis reveals a role of dimethyl-α-ketoglutarate in TGFβ-driven cytoskeleton regulation and myofibroblast differentiation

Go to EULAR Abstract Archive

Goals/Milestones

WP1: Determine metabolic dysregulation present in fibrotic SSc skin
WP2: Identify possible metabolic intermediates to interfere with profibrotic activation in SSc
WP3: Determine the effects of metabolic treatment on profibrotic activation of dermal fibroblasts
WP4: Extend analysis on fibrotic human skin
WP5: Present new data at international meetings
WP6: Submit a manuscript to a high impact journal