Community Research and Development Information Service - CORDIS

Final Report Summary - CX43-CRF (Implication of connexin 43 in chronic renal failure)

Chronic renal failure (CRF) represents one of the major causes of disability in western countries due to population’s aging, improved survival from cardiovascular diseases and spreading of type-2 diabetes. In the European Union over 7 million people are reported to be affected by CRF. Three hundred thousand of these are already being treated with renal replacement therapy, either by dialysis or transplantation, and the number requiring such treatment is progressively increasing each year. The relentless decline of renal function can be slowed down by anti-hypertensive therapies but they are partially effective. Thus, development of more effective and specific treatments for progressive renal failure is required in order to stop the progressing number of people affected by the disease.
The CRF process can be promoted by a variety of mechanisms including hypertension, diabetes or toxic injury. These pathologies may affect any of the kidney structures and are linked by their common ability to promote development of chronic inflammation leading to tissue sclerosis and to progressive decline of renal function.

Inflammation and excessive scaring are complex processes and have been recently associated with disruptions of gap junction-mediated intercellular communication (GJIC). Gap junctions are composed of intercellular channels that allow the direct exchange of small molecules between adjacent cells, this way synchronizing responses in multi-cellular organisms. This type of intercellular communication permits rapidly coordinated activities such as contraction of cardiac muscle but plays also a crucial role in slower physiological processes such as cell growth and development. Gap junction channels are formed by members of a family of related proteins called connexins (Cx) in vertebrates. There are more than 20 different types of Cx in the human and mouse genomes. Each type of connexin-made channel has unique permeabilities to various molecules. Thus, Cx composition of gap junctions appeared to determine channel selectivity.

Alterations of the expression of the major gap junction protein Cx43 have been associated to the development of inflammation in chronic vascular pathologies such as atherosclerosis. Inhibiting its expression protected vessels from the atherosclerotic plaque development and related diseases. However, little was known about the implication of this Cx in chronic renal pathologies. Thus the aim of our study was to investigate the role of Cx43 in an important degenerative pathology, the CRF.

For this purpose, we used different models characterized by an inflammatory response leading to chronic kidney disease.

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