Abstract
The studies outlined in this review highlight the relationship between inflammatory signaling molecules and connexin-43 (Cx43). Gap junction (GJ) channels and hemichannels (HCs) participate in the metabolic activity between intra- and extracellular space. Some ions and small molecules are exchanged from cell to cell or cell to extracellular space to affect the process of inflammation via GJ. We analyzed the effects of signaling molecules, such as innate immunity messengers, transcription factors, LPS, cytokine, inflammatory chemokines, and MMPs, on Cx43 expression during the inflammatory process. At the same time, we found that these signaling molecules play a critical role in the pathogenesis of keratitis. Thus, we assessed the function of Cx43 during inflammatory corneal disease. Corneal healing plays an essential role in the late stage of keratitis. We found that Cx43 is involved in wound healing. Studies have shown that the decrease of Cx43 can decrease the time of healing. We also report several Cx43 mimic peptides which can inhibit the activity of Cx43 Hc to mediate the releasing of adenosine triphosphate (ATP), which may in turn influence the inflammatory process.
Highlights
Gap junctions (GJs) appear at the cell plasma membrane and are formed by two interacting hemichannels (HCs) [1]
As are the cases with other inflammatory tissues, Cx43 and proinflammatory cytokines are involved in keratitis. Both the GJ and HC of Cx43 contribute to the inflammatory process in many tissues and, as cytokines and Cx43 are increased in infectious cornea, regulation of Cx43 might contribute to the development of this disease
Current studies have shown that GJs are involved in inflammatory responses and play an important role in this process
Summary
Gap junctions (GJs) appear at the cell plasma membrane and are formed by two interacting hemichannels (HCs) [1]. With the exception of intracellular communication, unopposed hemichannels (uHCs) can express only on the cell surface, providing exchange between the intra- and extracellular compartment, such as autocrine and paracrine signaling molecules. Nutrient, fluorescent glucose derivative, or signaling molecule IP3 can be transferred into cells via HCs [7] (Figure 1). HCs have been demonstrated to be regulated by diverse conditions including growth factors, proinflammatory cytokines, intracellular free Ca2+ levels, concentration of physiological extracellular cations, membrane potential, redox potential, protein phosphorylation, membrane stretch, alkalinization, acidification, hypoxia-reoxygenation, metabolic inhibition, and cellular nutrients (Figure 1) [7]. It is concluded that both the connexin mRNA and protein are expressed in central corneal and limbal epithelia [10]. Cx43 was found to participate in the development and normal physiology of the eye but is involved in corneal inflammation [3]
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