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Review
. 2022 Nov;22(11):2502-2508.
doi: 10.1111/ajt.17104. Epub 2022 Jun 10.

Connexins in endothelial cells as a therapeutic target for solid organ transplantation

Dinesh Jaishankar  1 , Kristen M Quinn  2 , Jes Sanders  1 , Leah Plumblee  2 , Thomas A Morinelli  2 , Satish N Nadig  1   2   3   4
Affiliations
Review

Connexins in endothelial cells as a therapeutic target for solid organ transplantation

Dinesh Jaishankar et al. Am J Transplant. 2022 Nov.

Abstract

Connexins are a class of membrane proteins widely distributed throughout the body and have various functions based on their location and levels of expression. More specifically, connexin proteins expressed in endothelial cells (ECs) have unique roles in maintaining EC barrier integrity and function-a highly regulated process that is critical for pro-inflammatory and pro-coagulant reactions. In this minireview, we discuss the regulatory influence connexin proteins have in maintaining EC barrier integrity and their role in ischemia-reperfusion injury as it relates to organ transplantation. It is evident that certain isoforms of the connexin protein family are uniquely positioned to have far-reaching effects on preserving organ function; however, there is still much to be learned of their roles in transplant immunology and the application of this knowledge to the development of targeted therapeutics.

Keywords: basic (laboratory) research/science; cellular biology; ischemia reperfusion injury (IRI); organ perfusion and preservation; solid organ transplantation; translational research/science.

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Figures

FIGURE 1
FIGURE 1
Immunological responses to allograft endothelium can lead to both acute and chronic rejection. Acute rejection occurs via a humoral response to donor antigens presented by graft ECs leading to inflammation, edema, and eventual graft thrombosis and failure. Chronic rejection is T cell–mediated: antigen‐presenting cells (APCs) recognize donor antigens leading to the activation of T cells in lymphatic organs that then migrate to allograft ECs and initiate the inflammatory cascade that results in graft failure (created with biorender.com).
FIGURE 2
FIGURE 2
Response of connexin hemichannels and gap junctions to ischemia–reperfusion injury. Hemichannels convert from the closed to the open configuration following a pathogenic response. This leads to the release of ATP which can then act on purinergic receptors on adjacent cells to promote calcium influx, cell edema, and the upregulation of pathways that lead to cell death. In comparison, gap junctions slowly close in response to ischemia as the intracellular levels of calcium increase, stores of ATP are depleted, and acidosis ensues. However, prior to closure intracellular signals are transported from one cell to adjacent cells via gap junctions which allow for the propagation of cell injury and death (created with biorender.com).
See this image and copyright information in PMC

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