# Mesothelial Cells in Fibrosis: Focus on Intercellular Crosstalk

## TL;DR

Mesothelial cells play a key role in fibrosis by interacting with other cell types, influencing tissue repair and disease progression.

## Contribution

The paper highlights the role of mesothelial cells in fibrosis through intercellular crosstalk and identifies potential therapeutic targets.

## Key findings

- Mesothelial cells contribute to fibrosis by undergoing MMT and promoting ECM remodeling.
- Bidirectional communication between mesothelial cells and fibroblasts, macrophages, and endothelial cells regulates fibrosis.
- Understanding mesothelial crosstalk reveals new antifibrotic therapy targets.

## Abstract

Mesothelial cells line serosal cavities and internal organs, playing a vital role in maintaining serosal integrity and homeostasis. Their remarkable plasticity and ability to undergo mesothelial-to-mesenchymal transition (MMT) position them as key regulators of tissue repair. However, when normal repair processes fail, mesothelial cells can acquire a profibrotic phenotype. They actively contribute to all stages of fibrosis development, including inflammation, fibrin accumulation, myofibroblast differentiation, and extracellular matrix (ECM) remodeling. Fibrotic progression involves multiple cell types, and communication among them is essential for its perpetuation. Mesothelial cells are implicated in bidirectional crosstalk with fibroblasts, macrophages, lymphocytes, and endothelial cells of the serosal microenvironment through direct contact, paracrine signaling, and extracellular vesicle exchange. These interactions regulate immune cell recruitment, cytokine balance, endothelial permeability, and ECM deposition, while, in turn, immune and endothelial cells modulate mesothelial activation, proliferation, and transition. Understanding this complex network of intercellular communication provides new insights into fibrosis pathogenesis and reveals promising targets for antifibrotic therapies.