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

Language

English

Publication Date

12-1-2025

Journal

APL Bioengineering

DOI

10.1063/5.0281447

PMID

41211122

PMCID

PMC12594547

PubMedCentral® Posted Date

11-6-2025

PubMedCentral® Full Text Version

Post-print

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.

Published Open-Access

yes

Recommended Citation

Nikitin, Pavel V; Chawla, Harshdeep S; Gutierrez, Jessica; et al., "ALK5 Inhibitor Impact on Bleomycin-Induced Systemic Sclerosis Mouse Model via Multifunctional Optical Coherence Tomography" (2025). Faculty, Staff and Student Publications. 3532.
https://digitalcommons.library.tmc.edu/uthmed_docs/3532