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June 20, 2025Journal of Clinical InvestigationOpen Access

Angiopoietin-like protein 2 mediates vasculopathy-driven fibrogenesis in a mouse model of systemic sclerosis

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Key result

Inhibiting endothelial cell junctional instability and vascular leakage with the synthetic metabolite UAS03 effectively mitigated ANGPTL2-driven vasculopathy and inhibited fibrogenesis in a mouse model of systemic sclerosis.

Why the study?

Vasculopathy is a common hallmark of fibrotic disorders including systemic sclerosis, but its underlying etiology and contribution to fibrogenesis remain ill defined.

Does UAS03 mitigate vasculopathy and inhibit fibrogenesis in a mouse model of systemic sclerosis?

Population

Snail transgenic mouse model of systemic sclerosis and endothelial cells

Comparison

Treatment with synthetic analog of microbial metabolite Urolithin A (UAS03)

Design

Preclinical animal and cellular study

Authors

DSDyuti SahaSTSujaya ThannimangalathSKSunny Kataria

Discussion

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Member takes

Overview

Hypothesis-generating for UAS03 in systemic sclerosis; human validation required before clinical consideration.

Structured PICO

Does UAS03 mitigate vasculopathy and inhibit fibrogenesis in a mouse model of systemic sclerosis?

P
Population
Mouse model (Snail-tg) and in vitro experiments investigating the role of ANGPTL2 in systemic sclerosis-associated vasculopathy and fibrogenesis.
I
Intervention
Synthetic analog of the microbial metabolite Urolithin A (UAS03)
O
Outcome
Mitigation of vasculopathy and inhibition of fibrogenesissurrogate

Inhibiting ANGPTL2-driven endothelial cell junctional instability with UAS03 mitigates vasculopathy and fibrogenesis in a mouse model of systemic sclerosis.

Limitations

  • The study primarily uses a mouse model which may not fully recapitulate all aspects of human systemic sclerosis.
  • Loss of vasculature (late stage disease) was not included in the study timeframe.

Cite This Study

Saha et al. (2025) studied Systemic sclerosis. UAS03 vs. Vehicle control was evaluated on Vascular leakage and dermal thickness. Inhibiting endothelial cell junctional instability and vascular leakage with the synthetic metabolite UAS03 effectively mitigated ANGPTL2-driven vasculopathy and inhibited fibrogenesis in a mouse model of systemic sclerosis.

synapsesocial.com/papers/6a97e18878a91a1f562d3006https://doi.org/10.1172/jci177123
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Also Consider

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

  1. 1Recent Insights into Cellular and Molecular Mechanisms of Defective Angiogenesis in Systemic Sclerosis2024 · 18 citations
  2. 2Nintedanib Attenuates Profibrotic Gene Expression in a 3D Organotypic Culture Model of Systemic Sclerosis Skin Fibrosis2026
  3. 3Angiotensin II in the lesional skin of systemic sclerosis patients contributes to tissue fibrosis via angiotensin II type 1 receptors2004 · 115 citations
  4. 4Human blood vessel organoids recapitulate key mechanisms of transition from vasculopathy to fibrosis in systemic sclerosis2026 · 1 citations
  5. 5The role and mechanism of CRISPLD2 in skin fibrosis of systemic sclerosis2024 · 1 citations