PhD Scientific Days 2025

Molecular Medicine V.

Spatiotemporal Analysis of ECM Remodelling in Chronic Intestinal Inflammation

Name of the presenter

Mógor Fruzsina

Institute/workplace of the presenter

Semmelweis University/Department of Anatomy, Histology and Embryology

Authors

Fruzsina Mógor¹, Dávid Dóra², Szilamér Ferenczi³

1: Semmelweis University/Department of Anatomy, Histology and Embryology
2: Semmelweis University, Department of Anatomy, Histology and Embryology
3: HUN-REN Institute of Experimental Medicine, Molecular Endocrinology

Text of the abstract

Introduction
Ulcerative colitis is a chronic inflammatory disease affecting the intestines. Recent studies highlight the crucial role of extracellular matrix (ECM) remodeling in driving inflammation. This study focuses on the ECM proteoglycans decorin (DCN) and biglycan (BGN), which, upon degradation, act as damage-associated molecular patterns (DAMPs), contributing to the inflammatory response.
Aims
We aim to investigate the spatial and temporal expression, degradation, and signaling of DCN and BGN during inflammation.
Methods
Using a dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we performed qPCR analysis to assess overall expression levels of DCN and BGN. We then analyzed single-cell RNA sequencing (scRNA-seq) data from DSS-treated and control mice using the Seurat package. Two separate datasets were examined: One exclusively covering the lamina muscularis layer. Another tracking changes over different time points throughout disease progression. Additionally, CellChat analysis was conducted to investigate intercellular communication in the scRNA-seq data.
Results
qPCR analysis revealed elevated DCN and BGN mRNA levels compared to controls. According to scRNA-seq data, the primary producers of DCN and BGN were type 2 cryptic fibroblasts (cCF2), though their intracellular expression remained unchanged during inflammation. However, expression levels of their degrading enzymes—matrix metalloproteinases (MMPs)—and their inhibitors (TIMPs) showed significant difference.
Comparing the two scRNA-seq datasets revealed distinct ECM-degrading enzyme profiles in the muscularis and mucosa layers. Longitudinal data further indicated that both degrading enzymes and their inhibitors peak on the same day. Additionally, CellChat analysis showed that inflammation induced an increase in TGF-β signaling as well as Fibronectin 1 (FN1) signaling in fibroblasts.
Conclusion
In summary, DCN and BGN are produced and degraded by cCF2 fibroblasts in the mouse colon, with the degradation process involving different enzymes in the mucosal and muscularis layers. Moreover, fibroblast responses to inflammation are modulated by TGF-β and FN1 signaling.
Funding
SUPPORTED BY THE EKÖP-2024-155 NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR CULTURE AND INNOVATION FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND.