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Functional Roles of Epithelial and Endothelial Cells
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Functional Roles of Epithelial and Endothelial Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 8313

Special Issue Editors

Prof. Dr. Lucie Germain

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Guest Editor
1. Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada
2. Regenerative Medicine Division, CHU de Québec—Université Laval Research Centre, Québec, QC G1J 1Z4, Canada
3. Université Laval Research Center on Experimental Organogenesis/LOEX, Québec, QC G1J 1Z4, Canada
Interests: regenerative medicine; tissue engineering; cell biology; cell therapy; gene therapy; cornea; skin
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Stéphanie Proulx

E-Mail Website
Guest Editor
1. Regenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, Canada
2. Département d’Ophtalmologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada
3. Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Hôpital Enfant-Jésus, 1401 18e Rue, Québec, QC G1V 0A6, Canada
Interests: cornea; tissue engineering

Special Issue Information

Dear Colleagues

Epithelial cells cover the surfaces of the body. For those that come into contact with the outside world, such as the skin and cornea, the epithelium protects the inner layers from external injuries that can arise from chemical, biological or physical insults. The importance of the epithelium is reinforced by the fact that the failed rapid closure of a wound can result in complications, such as scars, ulcers and infections. On the other hand, endothelial cells cover the inner surface of blood vessels (or the inner surface of the cornea for this specific tissue), forming a barrier that regulates exchanges between two structures. Apart from blood flow, the endothelium also plays key roles in immunology, inflammation, and angiogenesis. In the case of the corneal endothelium, endothelial dysfunctions result in excess fluid entering the stroma, causing vision loss.

In this Special Issue, reviews and articles will demonstrate the importance of epithelial and endothelial functionality in tissue homeostasis, mainly but not restricted to the skin and cornea, using 2D (cell cultured) and 3D (tissue-engineered) models. Topics related to the regulation of cellular processes, intercellular communication, signaling pathways, pump-leak balance, and barrier functionality are welcomed. 

Prof. Dr. Lucie Germain
Prof. Dr. Stéphanie Proulx
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epithelial cells
  • wound healing
  • endothelial cells
  • skin
  • cornea
  • functionality
  • barrier

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Published Papers (7 papers)

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10 pages, 1598 KiB  
Article
Drug-Dependent Inhibitory Effects on Corneal Epithelium Structure, Cell Viability, and Corneal Wound Healing by Local Anesthetics
by Sabine Foja, Joana Heinzelmann, Susanne Hünniger, Anja Viestenz, Christiane Rüger and Arne Viestenz
Int. J. Mol. Sci. 2024, 25(23), 13074; https://doi.org/10.3390/ijms252313074 - 5 Dec 2024
Viewed by 791
Abstract
Local anesthetics are commonly used in ophthalmic surgery. However, their use can affect the healing process. This study aimed to investigate the potential impact of anesthetic substances at clinically relevant concentrations and incubation times (3 min), specifically oxybuprocaine (OBPC, 0.4%), lidocaine (LIDO, 2%), [...] Read more.
Local anesthetics are commonly used in ophthalmic surgery. However, their use can affect the healing process. This study aimed to investigate the potential impact of anesthetic substances at clinically relevant concentrations and incubation times (3 min), specifically oxybuprocaine (OBPC, 0.4%), lidocaine (LIDO, 2%), and bupivacaine (BUPI, 0.5%), either alone or supplemented with hylase (HYLA, 30 I.E.), on corneal epithelium structure, cell viability, and wound healing. To assess the potential cytotoxicity of these anesthetic substances, viability and colony-forming efficiency (CFE) assays were conducted using the human telomerase-immortalized corneal epithelial (hTCEpi) cell line. Additionally, the toxicity of these substances was evaluated using a 3D human tissue-specific corneal epithelial construct as well as a porcine corneal culture model. The results indicate that OBPC (Novesine® 0.4%) exhibited significant cytotoxicity in 2D and 3D corneal epithelial cell culture models and delayed wound healing in the ex vivo porcine corneal organ culture model. In contrast, LIDO, BUPI, and HYLA were less cytotoxic to corneal cells, with no observed impact on wound healing in the porcine corneal organ culture model. In summary, local anesthetics commonly used in eye surgery are generally considered safe. However, the application of OBPC (Novesine® 0.4%) may delay wound healing. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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10 pages, 2739 KiB  
Article
The Inhibitory Effect of Hedera helix and Coptidis Rhizome Mixture in the Pathogenesis of Laryngopharyngeal Reflux: Cleavage of E-Cadherin in Acid-Exposed Primary Human Pharyngeal Epithelial Cells
by Nu-Ri Im, Byoungjae Kim, You Yeon Chung, Kwang-Yoon Jung, Yeon Soo Kim and Seung-Kuk Baek
Int. J. Mol. Sci. 2024, 25(22), 12244; https://doi.org/10.3390/ijms252212244 - 14 Nov 2024
Viewed by 830
Abstract
Laryngopharyngeal reflux disease (LPRD) is a prevalent upper airway disorder characterized by inflammation and epithelial damage due to the backflow of gastric contents. Current treatments, primarily proton pump inhibitors (PPIs), often show variable efficacy, necessitating the exploration of alternative or adjunctive therapies. This [...] Read more.
Laryngopharyngeal reflux disease (LPRD) is a prevalent upper airway disorder characterized by inflammation and epithelial damage due to the backflow of gastric contents. Current treatments, primarily proton pump inhibitors (PPIs), often show variable efficacy, necessitating the exploration of alternative or adjunctive therapies. This study investigates the therapeutic potential of a mixture of Hedera helix and Coptidis rhizome (HHCR) in mitigating the pathophysiological mechanisms of LPRD. Using an in vitro model of human pharyngeal epithelial cells exposed to acidic conditions, we observed that acid exposure significantly increased the expression of adenosine A3 receptor (adenosine A3) and matrix metalloproteinase-7 (MMP-7), leading to E-cadherin cleavage and compromised epithelial integrity. Treatment with the HHCR mixture effectively suppressed adenosine A3 expression and MMP-7 activity, thereby reducing E-cadherin cleavage and preserving cellular cohesion. These results highlight the HHCR mixture’s ability to modulate the adenosine A3–MMP-7–E-cadherin pathway, suggesting its potential as a valuable adjunctive therapy for LPRD, particularly for patients unresponsive to conventional PPI treatment. This study provides new insights into the molecular interactions involved in LPRD and supports further clinical evaluation of HHCR as a complementary treatment option. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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18 pages, 5056 KiB  
Article
A Small Intestinal Helminth Infection Alters Colonic Mucus and Shapes the Colonic Mucus Microbiome
by Thomas C. Mules, Francesco Vacca, Alissa Cait, Bibek Yumnam, Alfonso Schmidt, Brittany Lavender, Kate Maclean, Sophia-Louise Noble, Olivier Gasser, Mali Camberis, Graham Le Gros and Stephen Inns
Int. J. Mol. Sci. 2024, 25(22), 12015; https://doi.org/10.3390/ijms252212015 - 8 Nov 2024
Viewed by 1472
Abstract
Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. [...] Read more.
Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. In this study, we compare C57BL/6 mice infected with the small intestinal helminth Heligmosomoides polygyrus and uninfected controls to investigate changes in colonic mucus. Histology, gene expression, and immunofluorescent analysis demonstrate that this helminth induces goblet cell hyperplasia, and an upregulation of mucin sialylation, and goblet-cell-derived functional proteins resistin-like molecule-beta (RELM-β) and trefoil factors (TFFs), in the colon. Using IL-13 knockout mice, we reveal that these changes are predominantly IL-13-dependent. The assessment of the colonic mucus microbiome demonstrates that H. polygyrus infection increases the abundance of Ruminococcus gnavus, a commensal bacterium capable of utilising sialic acid as an energy source. This study also investigates a human cohort experimentally challenged with human hookworm. It demonstrates that TFF blood levels increase in individuals chronically infected with small intestinal helminths, highlighting a conserved mucus response between humans and mice. Overall, small intestinal helminths modify colonic mucus, highlighting this as a plausible mechanism by which human hookworm therapy could treat ulcerative colitis. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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12 pages, 2442 KiB  
Article
Factors Affecting the Density of Corneal Endothelial Cells Cultured from Donor Corneas
by Marina Bertolin, Alessandro Ruzza, Vanessa Barbaro, Elisa Zanetti, Diego Ponzin and Stefano Ferrari
Int. J. Mol. Sci. 2024, 25(22), 11884; https://doi.org/10.3390/ijms252211884 - 5 Nov 2024
Viewed by 890
Abstract
We investigated which specific correlation exists between the endothelial cell density (ECD) of corneal endothelial cell (CEC) cultures and the features of the donor corneas from which they originate. CEC cultures were prepared from one donor cornea or by pooling together cells of [...] Read more.
We investigated which specific correlation exists between the endothelial cell density (ECD) of corneal endothelial cell (CEC) cultures and the features of the donor corneas from which they originate. CEC cultures were prepared from one donor cornea or by pooling together cells of more corneas from elderly donors with ECDs lower or higher than 2000 cells/mm2. The ECDs of such primary cultures were evaluated and showed that that ECDs > 2000 cells/mm2 can be obtained only when CECs are isolated from (1) corneas of young donors; (2) at least two elderly donor corneas (if ECD > 2000 cells/mm2), or three elderly donor corneas (if ECD < 2000 cells/mm2). Secondary cultures are all characterized by ECDs < 2000 cells/mm2. Our study highlights the difficulties in obtaining cultures with ECDs > 2000 cells/mm2. Even if achievable with corneas from young donors, this becomes a challenging task when corneas from elderly donors are used (i.e., the overall majority of those collected by eye banks) and particularly when corneas from elderly donors with ECD < 2000 cells/mm2 are used. Pooling more of two corneas to obtain suitable CECs could technically overcome the problem. The above issues should be tackled appropriately before moving into clinical studies. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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10 pages, 603 KiB  
Article
Influence of Intraocular Pressure on the Expression and Activity of Sodium–Potassium Pumps in the Corneal Endothelium
by Princia Anney, Pascale Charpentier and Stéphanie Proulx
Int. J. Mol. Sci. 2024, 25(18), 10227; https://doi.org/10.3390/ijms251810227 - 23 Sep 2024
Viewed by 1348
Abstract
The corneal endothelium is responsible for pumping fluid out of the stroma in order to maintain corneal transparency, which depends in part on the expression and activity of sodium–potassium pumps. In this study, we evaluated how physiologic pressure and flow influence transcription, protein [...] Read more.
The corneal endothelium is responsible for pumping fluid out of the stroma in order to maintain corneal transparency, which depends in part on the expression and activity of sodium–potassium pumps. In this study, we evaluated how physiologic pressure and flow influence transcription, protein expression, and activity of Na+/K+-ATPase. Native and engineered corneal endothelia were cultured in a bioreactor in the presence of pressure and flow (hydrodynamic culture condition) or in a Petri dish (static culture condition). Transcription of ATP1A1 was assessed using qPCR, the expression of the α1 subunit of Na+/K+-ATPase was measured using Western blots and ELISA assays, and Na+/K+-ATPase activity was evaluated using an ATPase assay in the presence of ouabain. Results show that physiologic pressure and flow increase the transcription and the protein expression of Na+/K+-ATPase α1 in engineered corneal endothelia, while they remain stable in native corneal endothelia. Interestingly, the activity of Na+/K+-ATPase was increased in the presence of physiologic pressure and flow in both native and engineered corneal endothelia. These findings highlight the role of the in vivo environment on the functionality of the corneal endothelium. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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14 pages, 4738 KiB  
Article
Hepatocyte Growth Factor Modulates Corneal Endothelial Wound Healing In Vitro
by Merle Tratnig-Frankl, Nikolaus Luft, Guiseppe Magistro, Siegfried Priglinger, Andreas Ohlmann and Stefan Kassumeh
Int. J. Mol. Sci. 2024, 25(17), 9382; https://doi.org/10.3390/ijms25179382 - 29 Aug 2024
Viewed by 1221
Abstract
In this study, we assessed the impact of hepatocyte growth factor (HGF) on corneal endothelial cells (CECs), finding that HGF concentrations of 100–250 ng/mL significantly increased CEC proliferation by 30%, migration by 32% and improved survival under oxidative stress by 28% compared to [...] Read more.
In this study, we assessed the impact of hepatocyte growth factor (HGF) on corneal endothelial cells (CECs), finding that HGF concentrations of 100–250 ng/mL significantly increased CEC proliferation by 30%, migration by 32% and improved survival under oxidative stress by 28% compared to untreated controls (p < 0.05). The primary objective was to identify non-fibrotic pharmacological strategies to enhance corneal endothelial regeneration, addressing a critical need in conditions like Fuchs’ endothelial dystrophy (FED), where donor tissue is scarce. To confirm the endothelial nature of the cultured CECs, Na+/K+-ATPase immunohistochemistry was performed. Proliferation rates were determined through BrdU incorporation assays, while cell migration was assessed via scratch assays. Cell viability was evaluated under normal and oxidative stress conditions using WST-1 assays. To ensure that HGF treatment did not trigger epithelial-mesenchymal transition, which could lead to undesirable fibrotic changes, α-SMA staining was conducted. These comprehensive methodologies provided robust data on the effects of HGF, confirming its potential as a therapeutic agent for corneal endothelial repair without inducing harmful EMT, as indicated by the absence of α-SMA expression. These findings suggest that HGF holds therapeutic promise for enhancing corneal endothelial repair, warranting further investigation in in vivo models to confirm its clinical applicability. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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14 pages, 787 KiB  
Perspective
Endoplasmic Reticulum-Mitochondria Crosstalk in Fuchs Endothelial Corneal Dystrophy: Current Status and Future Prospects
by Anisha Kasi, William Steidl and Varun Kumar
Int. J. Mol. Sci. 2025, 26(3), 894; https://doi.org/10.3390/ijms26030894 - 22 Jan 2025
Viewed by 770
Abstract
Fuchs endothelial corneal dystrophy (FECD) is a progressive and debilitating disorder of the corneal endothelium (CE) that affects approximately 4% of individuals over the age of 40. Despite the burden of the disease, the pathogenesis of FECD remains poorly understood, and treatment options [...] Read more.
Fuchs endothelial corneal dystrophy (FECD) is a progressive and debilitating disorder of the corneal endothelium (CE) that affects approximately 4% of individuals over the age of 40. Despite the burden of the disease, the pathogenesis of FECD remains poorly understood, and treatment options are limited, highlighting the need for deeper investigation into its underlying molecular mechanisms. Over the past decade, studies have indicated independent contributions of endoplasmic reticulum (ER) and mitochondrial stress to the pathogenesis of FECD. However, there are limited studies suggesting ER-mitochondria crosstalk in FECD. Recently, our lab established the role of chronic ER stress in inducing mitochondrial dysfunction for corneal endothelial cells (CEnCs), indicating the existence of ER-mitochondria crosstalk in FECD. This paper aims to provide a comprehensive overview of the current understanding of how ER and mitochondrial stress contribute to FECD pathogenesis. The paper also reviews the literature on the mechanisms of ER-mitochondria crosstalk in other diseases relevant to FECD. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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