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Special Issue "Therapeutic Potential of Targeting Connexins in Managing Disease Onset and Progression 2.0"

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: 31 January 2023 | Viewed by 1764

Special Issue Editors

Prof. Dr. Paul Squires
E-Mail Website
Guest Editor
School of Life Sciences, University of Lincoln, Lincoln, UK
Interests: diabetes; cell-to-cell communication; connexins
Special Issues, Collections and Topics in MDPI journals
Dr. Claire Elizabeth Hills
E-Mail
Guest Editor
School of Life Sciences, University of Lincoln, Lincoln, UK
Interests: diabetes; cell-to-cell communication; connexins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cell contact, coupling, and communication are essential in maintaining normal physiological activity. Recent studies suggest that altered connexin expression and function are linked to remodeling of the extracellular matrix, integrin activation, and downstream purinergic signaling. As a consequence, changes in hemichannel and/or gap-junction connexin-mediated cell-to-cell communication are associated with inflammation and fibrosis, and have been linked to multiple diseases, including conditions of the heart, lung, liver, eye, and kidneys. In light of this, the potential impact of connexin-targeted therapeutics attracts considerable attention. In the current Special Issue, we will collectively highlight recent advances in the field of connexin biology, the link to disease development and progression, and the future therapeutic potential of connexin mimetics.

Prof. Dr. Paul Squires
Dr. Claire Elizabeth Hills
Guest Editors

Manuscript Submission Information

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Keywords

  • connexins
  • hemichannels
  • gap junctions
  • ATP
  • fibrosis
  • inflammation
  • purinergic
  • connexin mimetics
  • extracellular matrix

Published Papers (2 papers)

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Review

Review
The Role of Connexin 43 in Renal Disease: Insights from In Vivo Models of Experimental Nephropathy
Int. J. Mol. Sci. 2022, 23(21), 13090; https://doi.org/10.3390/ijms232113090 - 28 Oct 2022
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Abstract
Renal disease is a major public health challenge since its prevalence has continuously increased over the last decades. At the end stage, extrarenal replacement therapy and transplantation remain the only treatments currently available. To understand how the disease progresses, further knowledge of its [...] Read more.
Renal disease is a major public health challenge since its prevalence has continuously increased over the last decades. At the end stage, extrarenal replacement therapy and transplantation remain the only treatments currently available. To understand how the disease progresses, further knowledge of its pathophysiology is needed. For this purpose, experimental models, using mainly rodents, have been developed to unravel the mechanisms involved in the initiation and progression of renal disease, as well as to identify potential targets for therapy. The gap junction protein connexin 43 has recently been identified as a novel player in the development of kidney disease. Its expression has been found to be altered in many types of human renal pathologies, as well as in different animal models, contributing to the activation of inflammatory and fibrotic processes that lead to renal damage. Furthermore, Cx43 genetic, pharmacogenetic, or pharmacological inhibition preserved renal function and structure. This review summarizes the existing advances on the role of this protein in renal diseases, based mainly on different in vivo animal models of acute and chronic renal diseases. Full article
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Review
Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes
Int. J. Mol. Sci. 2022, 23(2), 600; https://doi.org/10.3390/ijms23020600 - 06 Jan 2022
Cited by 2 | Viewed by 1252
Abstract
Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working [...] Read more.
Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function. Full article
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