Expression and role of connexin-based gap junctions in pulmonary inflammatory diseases

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• 作者：Vé ; ronique Freund-Michel^a ; ^b ; ^{veronique.michel@u-bordeaux.fr" class="auth_mail" title="E-mail the corresponding author} ; Bernard Muller^a ; ^b ; Roger Marthan^a ; ^b ; ^c ; Jean-Pierre Savineau^a ; ^b ; Christelle Guibert^a ; ^b
• 关键词：ADMA ; asymmetric dimethylarginine ; cAMP ; cyclic adenosine monophosphate ; CD73 ; cluster of differentiation 73 ; CDC2 ; cell division cycle 2 ; CFTR ; cystic fibrosis transmembrane conductance regulator ; cGMP ; cyclic guanosine monophosphate ; CH ; chronic hypoxia ; CH rats ; rats subjected to chronic hypoxia ; CK1 ; casein kinase 1 ; Cx ; connexin ; HPV ; hypoxic pulmonary vasoconstriction ; IP3 ; inositol triphosphate ; LPS ; lipopolysaccharide ; MAPK ; mitogen-activated protein kinase ; MCT ; monocrotaline ; MCT rats
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：164
• 期：Complete
• 页码：105-119
• 全文大小：2635 K

文摘

Connexins are transmembrane proteins that can generate intercellular communication channels known as gap junctions. They contribute to the direct movement of ions and larger cytoplasmic solutes between various cell types. In the lung, connexins participate in a variety of physiological functions, such as tissue homeostasis and host defence. In addition, emerging evidence supports a role for connexins in various pulmonary inflammatory diseases, such as asthma, pulmonary hypertension, acute lung injury, lung fibrosis or cystic fibrosis. In these diseases, the altered expression of connexins leads to disruption of normal intercellular communication pathways, thus contributing to various pathophysiological aspects, such as inflammation or tissue altered reactivity and remodeling.

The present review describes connexin structure and organization in gap junctions. It focuses on connexins in the lung, including pulmonary bronchial and arterial beds, by looking at their expression, regulation and physiological functions. This work also addresses the issue of connexin expression alteration in various pulmonary inflammatory diseases and describes how targeting connexin-based gap junctions with pharmacological tools, synthetic blocking peptides or genetic approaches, may open new therapeutic perspectives in the treatment of these diseases.