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January 16, 2023International Journal of Molecular SciencesOpen Access

Biglycan Involvement in Heart Fibrosis: Modulation of Adenosine 2A Receptor Improves Damage in Immortalized Cardiac Fibroblasts

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Key result

Treatment with A2AR antagonists Istradefylline and ZM241385 reduced oxidative stress and decreased the expression of fibrotic markers including collagen1a1, BGN, and α-SMA in TGF-β-stimulated cardiac fibroblasts.

Why the study?

To investigate the possible crosstalk between A2AR and biglycan modulation in an in vitro model of TGF-β-induced cardiac fibrosis.

Population

Immortalized human cardiac fibroblasts stimulated with TGF-β

Comparison

Istradefylline vs ZM241385 vs untreated TGF-β-challenged cells

Design

In vitro controlled laboratory study

Follow-up

24 h

Authors

MSMichele ScuruchiUniversity of MessinaFMFederica ManninoUniversity of MessinaCIChiara ImbesiUniversity of Messina

Discussion

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Member takes

Overview

BGN may regulate fibroblast phenotype in fibrosis; hypothesis-generating for targeted therapies, clinical translation unproven.

Structured PICO

P
Population
In vitro study using immortalized human cardiac fibroblasts stimulated with TGF-β to induce a fibrotic phenotype.
I
Intervention
A2AR antagonists (Istradefylline 10 µM or ZM241385 1 µM) for 24 h
C
Comparator
TGF-β-challenged fibroblasts without A2AR antagonist treatment
O
Outcome
Intracellular reactive oxygen species (ROS) and gene/protein expression of fibrotic markers (collagen1a1, MMPs 3/9, BGN, caspase-1, IL-1β, SMAD3, α-SMA, phospho-Akt)surrogate

A2AR antagonism attenuates TGF-β-induced fibrotic processes and oxidative stress in human cardiac fibroblasts, highlighting a potential therapeutic target for pathological cardiac remodeling.

Cite This Study

Scuruchi et al. (2023) studied Cardiac fibrosis. A2AR antagonists (Istradefylline and ZM241385) vs. TGF-β-challenged human fibroblasts without A2AR antagonist was evaluated on Oxidative stress (ROS reduction) and gene/protein expression of fibrotic markers. Treatment with A2AR antagonists Istradefylline and ZM241385 reduced oxidative stress and decreased the expression of fibrotic markers including collagen1a1, BGN, and α-SMA in TGF-β-stimulated cardiac fibroblasts.

synapsesocial.com/papers/6a7be0d72305edf9bbed2856https://doi.org/10.3390/ijms24021784
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1β3‐ AR /β‐arrestin2 Interaction Triggers Cardiac Fibrosis Through JNK /c‐Jun Pathway in Cardiac Fibroblasts2026
  2. 2Deficiency of Biglycan Causes Cardiac Fibroblasts to Differentiate into a Myofibroblast Phenotype2011 · 65 citations
  3. 3Stimulation of Adenosine A2B Receptor Inhibits Endothelin-1-Induced Cardiac Fibroblast Proliferation and α-Smooth Muscle Actin Synthesis Through the cAMP/Epac/PI3K/Akt-Signaling Pathway2017 · 57 citations
  4. 4Cardiac myocyte β3-adrenergic receptors prevent myocardial fibrosis by modulating oxidant stress-dependent paracrine signaling2017 · 79 citations
  5. 5The role of TGF-β in cardiac fibrosis and heart failure: A review2024 · 8 citations