New Insights into Mesothelial Cells

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 January 2026) | Viewed by 2475

Special Issue Editors


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Guest Editor
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milano, MI, Italy
Interests: pleural liquid; pleural friction; alveolar cells; mesothelial cells; mesothelial transport
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milano, MI, Italy
Interests: epithelial and mesothelial barriers; fluid, ion and polypeptide transports; MALT; pleural liquid; pleural friction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The only function of mesothelial cells was traditionally thought to be lining the body's serous cavities and synthesizing lubricating fluids in order to create a non-adhesive surface that reduces friction between organs. However, mesothelial cells are now recognized to play a variety of fascinating roles, leading to new insights into their biological significance and potential in medical applications.

Mesothelial cells are characterized by great plasticity: they can undergo the epithelial-to-mesenchymal transition (EMT), which plays a key role in the onset of fibrosis and serous cavity adhesion in stressful conditions. Mesothelial cells have also been shown to play an important role in the regeneration of damaged tissue. When injury occurs in serous membranes, these cells can migrate to the injury site and proliferate to aid in tissue repair. Mesothelial cells also have stem cell-like properties, as they can retain the ability to differentiate into various cytotypes, including osteoblasts and adipocytes.

Another role of mesothelial cells is their ability to modulate immune responses. They can release substances that attract immune cells into serous cavities to fight infections and prevent the spread of pathogens.

Mesothelial cells are a focus in cancer research, especially concerning mesothelioma, a cancer originating in the mesothelium. Beyond this, in recent years, numerous studies have highlighted the role of mesothelial cells in promoting the dissemination and growth of cancer cells in serous cavities, making them significant players in the tumor microenvironment. Additionally, mesothelial cells might also lead to resistance to anti-tumor drugs, indicating that they are potential targets for cancer therapies.

This Special Issue aims to cover the above-described topics. We will publish communications, full papers and reviews focused on all-novel insights concerning mesothelial cells, with an emphasis on their molecular mechanism.

Dr. Francesca Bodega
Dr. Cristina Porta
Guest Editors

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Keywords

  • mesothelial cells
  • serous cavities
  • lubricating fluids
  • epithelial–mesenchymal transition
  • fibrosis
  • tissue repair
  • mesothelioma
  • tumor microenvironment
  • immune response

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Published Papers (3 papers)

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Research

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18 pages, 6886 KB  
Article
Spiny Mice Show a Profibrotic Epicardial Mesothelial Response to Hypoxic Injury Comparable to C57BL/6 Mice
by Konstantin Dergilev, Aleria Dolgodvorova, Zoya Tsokolaeva, Irina Iarushkina, Irina Beloglazova, Yulia Goltseva and Yelena Parfyonova
Biomolecules 2026, 16(5), 717; https://doi.org/10.3390/biom16050717 (registering DOI) - 13 May 2026
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Abstract
Epicardial mesothelium plays a pivotal role in postinfarction cardiac repair by generating fibroblasts, producing extracellular matrix, and releasing paracrine mechanisms. However, interspecies differences have not been sufficiently studied, particularly in in vivo models of scar-free healing such as the African spiny mouse ( [...] Read more.
Epicardial mesothelium plays a pivotal role in postinfarction cardiac repair by generating fibroblasts, producing extracellular matrix, and releasing paracrine mechanisms. However, interspecies differences have not been sufficiently studied, particularly in in vivo models of scar-free healing such as the African spiny mouse (Acomys cahirinus). This study aimed to compare the profibrotic response of epicardial mesothelial cells (MCs) from Acomys and C57BL/6 mice to hypoxic stress, a key factor in postinfarction recovery. We isolated epicardial MCs from the African spiny mouse (Acomys cahirinus), a species with documented cardiac regenerative capabilities, and from C57BL/6 laboratory mice. Using a CoCl2-induced hypoxia model in vitro, we assessed cell viability, morphological changes, and expression of epithelial and fibroblast markers. In vivo, following experimental myocardial infarction (MI), we evaluated tissue hypoxia (pimonidazole adducts), epicardial activation (layer thickness, Wt1+ and TBX18+ progenitor cells), and collagen accumulation. The study was conducted using real-time PCR, Western blotting, immunohistochemical analysis and microscopic examination. In vitro, MCs from both species exhibited an epithelial-like phenotype under normoxic conditions, expressing E-cadherin and cytokeratin 18. Hypoxia (200 µM CoCl2) induced a comparable response in both Acomys and C57BL/6 cells, characterized by a shift to a spindle-shaped, fibroblast-like morphology, decreased E-cadherin expression, and increased pro-collagen 1 and α-SMA expression. Following MI, both species exhibited similarly extensive hypoxic areas affecting the epicardial zone. Epicardial activation dynamics were comparable: from day 3 post-MI, epicardial thickness increased significantly, and Wt1+ and TBX18+ progenitor cells accumulated, peaking during the first week. Collagen accumulation in the epicardial region was similar between species, although the number of Wt1+ cells was higher in C57BL/6 on day 7. Despite the well-known superior regenerative capacity of spiny mice, epicardial MCs from Acomys and C57BL/6 demonstrated similar signs of profibrotic responses to hypoxic stimulation both in vitro and following MI. These findings suggest that species-specific regenerative outcomes may not be attributable to differential acute epicardial sensitivity to hypoxia, but rather to downstream mechanisms or additional factors influencing the cardiac repair process. This study provides the first characterization of Acomys epicardial MCs and establishes a foundation for further investigation of evolutionarily conserved and species-specific mechanisms of cardiac regeneration. Full article
(This article belongs to the Special Issue New Insights into Mesothelial Cells)
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Review

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21 pages, 1320 KB  
Review
Mesothelial Cells in Fibrosis: Focus on Intercellular Crosstalk
by Nadezhda Bakalenko, Evdokiya Kuznetsova, Konstantin Dergilev, Irina Beloglazova and Anna Malashicheva
Biomolecules 2026, 16(1), 85; https://doi.org/10.3390/biom16010085 - 5 Jan 2026
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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 [...] Read more.
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. Full article
(This article belongs to the Special Issue New Insights into Mesothelial Cells)
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Other

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10 pages, 4806 KB  
Brief Report
Optimized Method for Establishing Primary Human Mesothelial Cell Cultures Preserving Epithelial Phenotype
by Evdokiya Kuznetsova, Nadezhda Bakalenko, Liana Gaifullina, Mikhail Atyukov, Konstantin Dergilev, Irina Beloglazova and Anna Malashicheva
Biomolecules 2025, 15(12), 1669; https://doi.org/10.3390/biom15121669 - 30 Nov 2025
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Abstract
Mesothelial cells (MCs) are highly relevant for studying the pathogenesis of serosal diseases, fibrosis, inflammation, and tumor progression. However, the isolation and maintenance of an epithelial-like phenotype of MCs in vitro remain methodologically challenging due to their tendency to undergo mesothelial-to-mesenchymal transition (MMT). [...] Read more.
Mesothelial cells (MCs) are highly relevant for studying the pathogenesis of serosal diseases, fibrosis, inflammation, and tumor progression. However, the isolation and maintenance of an epithelial-like phenotype of MCs in vitro remain methodologically challenging due to their tendency to undergo mesothelial-to-mesenchymal transition (MMT). In this work, we propose a combined protocol utilizing collagen IV coating, conditioned medium, and short-term ROCK inhibitor treatment, which improves cell survival. This approach enables the establishment of primary human cultures suitable for investigating mesothelial cell functional activity and for assessing the efficacy of potential therapeutic strategies. Full article
(This article belongs to the Special Issue New Insights into Mesothelial Cells)
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