Fibrotic remodeling in the NOD/ShiLtJ mouse model of Sjögren’s disease: insights from single-cell transcriptomics and AI-driven ECM quantification - Report - MDSpire
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Exploring Fibrotic Changes in the NOD/ShiLtJ Mouse Model of Sjögren’s Disease: Insights from Single-Cell Transcriptomics and AI-Enhanced ECM Analysis
Clinical Report: Exploring Fibrotic Changes in the NOD/ShiLtJ Mouse Model of Sjögren’s Disease
Overview
This study investigates the role of fibrosis in Sjögren's Disease using the NOD/ShiLtJ mouse model.
Background
Sjögren's Disease (SjD) is an autoimmune disorder that significantly impacts quality of life through symptoms such as dry mouth and dry eyes. Understanding the mechanisms of fibrosis in SjD is crucial, as fibrosis contributes to glandular dysfunction and is less understood compared to inflammation. The NOD/ShiLtJ mouse model provides a valuable platform for studying these fibrotic changes.
Data Highlights
Measurement
Control Mice
NOD/ShiLtJ Mice
Col1a1 Levels
Baseline
Increased
Col1a2 Levels
Baseline
Increased
Col3a1 Levels
Baseline
Increased
Fibrosis Severity
Low
High
Nintedanib Treatment Effect
None
Modest Reduction
Key Findings
Fibroblast populations in NOD/ShiLtJ mice showed increased ECM gene expression compared to controls.
Significant fibrotic remodeling was observed in the periacinar ECM of salivary glands.
Fibrosis severity correlated with the diabetic phenotype of the NOD/ShiLtJ strain.
Both periductal and periacinar fibrosis progressed with age in these mice.
Nintedanib treatment resulted in modest reductions in multiple fibrotic indices over 8 weeks.
Clinical Implications
Further research is needed to explore the long-term effects and clinical applicability of antifibrotic treatments in Sjögren's Disease.
Conclusion
This study establishes the NOD/ShiLtJ mouse model as a relevant system for studying SjD-associated fibrosis.
by Jennifer M. Morrissey, Deirdre A. Nelson, Li Chen, Mathieu Petitjean, Joey R. Tavarez, Amber L. Altrieth-Flagg, Nicholas L. Moskwa, Renae Williams-Atkinson, Ben Fowler, Rafael Pena, Kennedi Weston, Nikhita Kumar, Nathan Aist, Melinda Larsen