# ALK5 inhibitor impact on bleomycin-induced systemic sclerosis mouse model via multifunctional optical coherence tomography

**Authors:** Pavel V. Nikitin, Harshdeep S. Chawla, Jessica Gutierrez, Geethangili Madamanchi, Manmohan Singh, Salavat R. Aglyamov, Minghua Wu, Jerry Alonso, Matthew Fronheiser, Juliana Coculo, Shuyan Du, Shervin Assassi, Kirill V. Larin

PMC · DOI: 10.1063/5.0281447 · 2025-11-06

## TL;DR

This study uses optical coherence tomography to monitor skin changes in a mouse model of systemic sclerosis and tests an inhibitor's effect on reversing these changes.

## Contribution

The study introduces a multifunctional OCT approach for noninvasive, longitudinal monitoring of SSc progression and treatment response.

## Key findings

- Bleomycin treatment increased skin thickness, stiffness, and vessel lumen width in the mouse model.
- SB 525334 partially reversed these structural and vascular changes, indicating potential therapeutic benefit.
- Multifunctional OCT methods showed feasibility for monitoring SSc pathogenesis and treatment efficacy.

## Abstract

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis, vascular dysfunction, and immune dysregulation, leading to significant morbidity and mortality. Noninvasive imaging techniques are critical for monitoring disease progression and evaluating therapeutic interventions. This study investigates the technical feasibility of multifunctional optical coherence tomography (OCT)-based methods for longitudinal assessment of skin thickness, stiffness, and microvasculature in a murine SSc model as a translational, noninvasive, and quantitative method to study disease progression and treatment response. Our findings demonstrate significant structural, biomechanical, and vascular changes in the skin's stiffness, indicative of fibrosis, a hallmark of SSc. The application of SB 525334 (a transforming growth factor β1 receptor ALK5 inhibitor) mitigated these changes, highlighting its potential as a treatment strategy. Despite the inherent limitations of the mouse model in replicating the complexity of SSc, this study introduces a new technique for investigating the SSc pathogenesis and evaluating the efficacy of potential SSc therapies. These results encourage further exploration of the multifunctional Optical Coherence Elastography and OCT Angiography for monitoring disease progression and treatment response in SSc. In summary, bleomycin treatment significantly increased skin thickness, stiffness, and vessel lumen width, while SB 525334 partially reversed these changes, demonstrating the feasibility of our multifunctional OCT approach for monitoring experimental SSc.

## Linked entities

- **Chemicals:** SB 525334 (PubChem CID 9967941), bleomycin (PubChem CID 5360373)
- **Diseases:** Systemic sclerosis (MONDO:0005100), SSc (MONDO:0005100)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tgfbr1 (transforming growth factor, beta receptor I) [NCBI Gene 21812] {aka ALK5, Alk-5, ESK2, TGFR-1, TbetaR-I, TbetaRI}
- **Diseases:** vascular dysfunction (MESH:D002561), fibrosis (MESH:D005355), autoimmune disease (MESH:D001327), SSc (MESH:D012595), immune dysregulation (OMIM:614878)
- **Chemicals:** bleomycin (MESH:D001761), SB 525334 (MESH:C521813)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12594547/full.md

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Source: https://tomesphere.com/paper/PMC12594547