Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Connexins Multifaceted Aspects in Homeostasis and Disease

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 11003

Share This Special Issue

Special Issue Editors

Dr. Rosalba Parenti

E-Mail Website
Guest Editor

Department of Biomedical and Biotechnological Sciences (BIOMETC), Section of Physiology, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Interests: physiology; morphology; molecular pathology
Special Issues, Collections and Topics in MDPI journals

Dr. Nunzio Vicario

E-Mail Website
Co-Guest Editor

Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Interests: compensatory changes; reactive gliosis; connexin; neuroinflammation; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Connexin intercellular channels represent the physiological substrate allowing direct intercellular communication in living organisms to permit the coordination of cellular activities and control cell growth, differentiation, and maintenance of tissue homoeostasis. Connexin dysregulation is emerging as a critical process in the escape from the delicate balance of multicellular microenvironments during disease development, including neurodegeneration, organ dysfunction, and tumor progression. Increasing knowledge of Connexins-related processes, from regulators of their function to the influence they exert on different signaling pathways, indicates that Connexin plays a multifaceted role in determining both life and cell death conditions.

This Special Issue, “Connexins multifaceted aspects in homeostasis and disease”, aims to collect original research manuscripts, short communications, and reviews on the latest progress uncovering mechanisms and strategies for connexin targeting in both channel-dependent and -independent functions. Indeed, a detailed analysis of the pathophysiology of Connexin could represent a strategic link in the growing urgency to develop a molecular signature towards personalized medicine.

Dr. Rosalba Parenti
Dr. Nunzio Vicario
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at mdpi.longhoe.net by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

Connexin
gap junction
hemichannels
intercellular communication
signaling
homeostasis
imaging
animal model
inflammation
oxidative stress

Published Papers (5 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

15 pages, 6357 KiB

Open AccessArticle

Downregulation of the Astroglial Connexin Expression and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

by Anna Andrioli, Paolo Francesco Fabene, Giuseppa Mudò, Vincenza Barresi, Valentina Di Liberto, Monica Frinchi, Marina Bentivoglio and Daniele Filippo Condorelli

Int. J. Mol. Sci. 2023, 24(1), 23; https://doi.org/10.3390/ijms24010023 - 20 Dec 2022

Cited by 18 | Viewed by 1476

Abstract

Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the effect of seizures on Cx expression is controversial. The present study focused on the response of Cxs to status epilepticus (SE), which is in turn an epileptogenic insult. The expression of neuronal Cx36 and astrocytic Cx30 and Cx43 mRNAs was investigated in the brain of rats in the first day after pilocarpine-induced SE. In situ hybridization revealed a progressive decrease in Cx43 and Cx30 mRNA levels, significantly marked 24 h after SE onset in neocortical areas and the hippocampus, and in most thalamic domains, whereas Cx36 mRNA did not exhibit obvious changes. Regional evaluation with quantitative real-time-RT-PCR confirmed Cx43 and Cx30 mRNA downregulation 24 h after SE, when ongoing neuronal cell death was found in the same brain regions. Immunolabeling showed at the same time point marked a decrease in Cx43, microglia activation, and interleukin-1β induction in some microglial cells. The data showed a transient downregulation of astroglial Cxs in the cortical and thalamic areas in which SE triggers neurodegenerative events in concomitance with microglia activation and cytokine expression. This could potentially represent a protective response of neuroglial networks to SE-induced acute damage. Full article

(This article belongs to the Special Issue Connexins Multifaceted Aspects in Homeostasis and Disease)

► Show Figures

Figure 1

16 pages, 2176 KiB

Open AccessArticle

Apelin-13 Increases Functional Connexin-43 through Autophagy Inhibition via AKT/mTOR Pathway in the Non-Myocytic Cell Population of the Heart

by Emanuela Vitale, Rachele Rosso, Marco Lo Iacono, Caterina Cristallini, Claudia Giachino and Raffaella Rastaldo

Int. J. Mol. Sci. 2022, 23(21), 13073; https://doi.org/10.3390/ijms232113073 - 28 Oct 2022

Cited by 6 | Viewed by 1649

Abstract

Studies have shown a link between the downregulation of connexin 43 (Cx43), the predominant isoform in cardiac gap junctions, and high susceptibility to cardiac arrhythmias and cardiomyocyte death. Non-myocytic cells (NMCs), the most abundant component of the heart, exert multiple cardiac functions and represent an important therapeutic target for diseased cardiac tissue. A few studies have investigated the effect of Apelin-13, an endogenous peptide with a key role in various cardiovascular functions, on Cx43 expression in cardiomyocytes. However, it remained unknown whether Apelin-13 influences Cx43 expression in NMCs. Here, we found that in NMCs, Cx43 protein expression increased after Apelin-13 treatment (100 nM for 48 h). Furthermore, dye transfer assays proved that Apelin-13-treated NMCs had a greater ability to communicate with surrounding cardiomyocytes, and this effect was abrogated by carbenoxolone, a gap junction inhibitor. Interestingly, we showed that Apelin-13 increased Cx43 through autophagy inhibition, as proved by the upregulation of p62 and LC3I, acting as 3-MA, a well-known autophagy inhibitor. In addition, Apelin-13-induced AKT and mTOR phosphorylation was abolished by LY294002 and rapamycin inhibitors resulting in Cx43 increased suppression. These results open the possibility of targeting gap junctions in NMCs with Apelin-13 as an exciting therapeutic approach with great potential. Full article

(This article belongs to the Special Issue Connexins Multifaceted Aspects in Homeostasis and Disease)

► Show Figures

Figure 1

Review

Jump to: Research

18 pages, 1588 KiB

Open AccessReview

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

by Yan-Jun Zong, **ao-Zhou Liu, Lei Tu and Yu Sun

Int. J. Mol. Sci. 2023, 24(12), 10349; https://doi.org/10.3390/ijms241210349 - 19 Jun 2023

Cited by 3 | Viewed by 1981

Abstract

The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6, respectively, are the most abundantly expressed connexins in the inner ear. Connexin 43, which is encoded by GJA1, appears to be widely expressed in various organs, including the heart, skin, the brain, and the inner ear. The mutations that arise in GJB2, GJB6, and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns. As it is predicted that connexins include at least 20 isoforms in humans, the biosynthesis, structural composition, and degradation of connexins must be precisely regulated so that the gap junctions can properly operate. Certain mutations result in connexins possessing a faulty subcellular localization, failing to transport to the cell membrane and preventing gap junction formation, ultimately leading to connexin dysfunction and hearing loss. In this review, we provide a discussion of the transport models for connexin 43, connexins 30 and 26, mutations affecting trafficking pathways of these connexins, the existing controversies in the trafficking pathways of connexins, and the molecules involved in connexin trafficking and their functions. This review can contribute to a new way of understanding the etiological principles of connexin mutations and finding therapeutic strategies for hereditary deafness. Full article

(This article belongs to the Special Issue Connexins Multifaceted Aspects in Homeostasis and Disease)

► Show Figures

Figure 1

16 pages, 1347 KiB

Open AccessReview

Functional Roles of Connexins and Gap Junctions in Osteo-Chondral Cellular Components

by Agata Zappalà, Ivana Roberta Romano, Floriana D’Angeli, Giuseppe Musumeci, Debora Lo Furno, Rosario Giuffrida and Giuliana Mannino

Int. J. Mol. Sci. 2023, 24(4), 4156; https://doi.org/10.3390/ijms24044156 - 19 Feb 2023

Cited by 5 | Viewed by 2356

Abstract

Gap junctions (GJs) formed by connexins (Cxs) play an important role in the intercellular communication within most body tissues. In this paper, we focus on GJs and Cxs present in skeletal tissues. Cx43 is the most expressed connexin, participating in the formation of both GJs for intercellular communication and hemichannels (HCs) for communication with the external environment. Through GJs in long dendritic-like cytoplasmic processes, osteocytes embedded in deep lacunae are able to form a functional syncytium not only with neighboring osteocytes but also with bone cells located at the bone surface, despite the surrounding mineralized matrix. The functional syncytium allows a coordinated cell activity through the wide propagation of calcium waves, nutrients and anabolic and/or catabolic factors. Acting as mechanosensors, osteocytes are able to transduce mechanical stimuli into biological signals that spread through the syncytium to orchestrate bone remodeling. The fundamental role of Cxs and GJs is confirmed by a plethora of investigations that have highlighted how up- and downregulation of Cxs and GJs critically influence skeletal development and cartilage functions. A better knowledge of GJ and Cx mechanisms in physiological and pathological conditions might help in develo** therapeutic approaches aimed at the treatment of human skeletal system disorders. Full article

(This article belongs to the Special Issue Connexins Multifaceted Aspects in Homeostasis and Disease)

► Show Figures

Figure 1

16 pages, 2046 KiB

Open AccessReview

Connexins Signatures of the Neurovascular Unit and Their Physio-Pathological Functions

by Nunzio Vicario and Rosalba Parenti

Int. J. Mol. Sci. 2022, 23(17), 9510; https://doi.org/10.3390/ijms23179510 - 23 Aug 2022

Cited by 7 | Viewed by 2931

Abstract

Central nervous system (CNS) homeostasis is closely linked to the delicate balance of the microenvironment in which different cellular components of the neurovascular unit (NVU) coexist. Intercellular communication plays a pivotal role in exchanges of signaling molecules and mediators essential for survival functions, as well as in the removal of disturbing elements that can lead to related pathologies. The specific signatures of connexins (Cxs), proteins which form either gap junctions (GJs) or hemichannels (HCs), represent the biological substrate of the pathophysiological balance. Connexin 43 (Cx43) is undoubtedly one of the most important factors in glia–neuro–vascular crosstalk. Herein, Cxs signatures of every NVU component are highlighted and their critical influence on functional processes in healthy and pathological conditions of nervous microenvironment is reviewed. Full article

(This article belongs to the Special Issue Connexins Multifaceted Aspects in Homeostasis and Disease)

► Show Figures

Journal Menu

Journal Browser

Connexins Multifaceted Aspects in Homeostasis and Disease

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI