CCN1 expression in interleukin-6 deficient mouse kidney in experimental model of heart failure

Abstract

Chronic heart failure often leads to worsening of the renal function. Mediators of this process include inflammatory and neuroendocrine factors. CCN1 (Cyr 61), a member of growth factor-inducible immediate early genes, which modulates inflammation and fibrogenesis, is excreted with urine in the early phase of acute renal injury and may be involved in the pathogenesis of the cardiorenal syndrome. The aim of the study was to evaluate CCN1 protein abundance and localization in the kidney of IL-6-deficient C57BL/6J (IL-6 KO) mice and respective wild-type (WT) animals in basal conditions and in animals with chronic heart failure twelve weeks after myocardial infarction. Age-and sex-matched mice from both strains subjected to sham operation served as controls. One group of WT animals subjected to myocardial infarction was treated with antagonist of AT1 receptor telmisartan over 12 weeks. Abundance and localization of CCN1 protein in kidney were assessed with Western blotting and immunohistochemistry, respectively. In all groups the strongest immunohistochemical reaction for CCN1 was observed in distal convoluted tubules and in smaller arteries, however, the total expression of CCN1 protein was lower in IL-6 KO mice in comparison to WT animals. The main difference in CCN1 distribution between the examined genotypes was lack of reaction in internal renal medulla and very weak reaction in proximal convoluted tubules in IL-6 KO mice. Experimental heart failure only slightly attenuated the expression of CCN1 protein in the kidney of WT mice and had no effect in IL-6 KO mice. Although, blockade of AT1 receptor did not alter CCN1 protein expression in kidneys of WT mice after myocardial infarction, it significantly changed its CCN1 distribution in the renal tubular system. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 84-91)

IL-6 deficiency attenuates p53 protein accumulation in aged male mouse hippocampus

“…One, randomly taken left or right hippocampus was used for Western blot, while the other for quantitative Real-Time PCR. Genotype of mice was confirmed by polymerase chain reaction as described previously (Bonda et al 2013).…”

Association between CCN1 gene polymorphism and acute coronary syndrome in Chinese Han and Uygur populations

“…Moreover, the elevated CCN1 levels were significantly associated with the severity of acute heart failure in a cohort of 183 patients [8]. In addition, animal heart failure experiments also revealed that the expression of CCN1 protein was increased [9][10][11].…”

Emerging role of CCN family proteins in fibrosis

“…There is mounting evidence that CCN1 plays critical roles in cardiovascular development, embryogenesis, wound healing, inflammation regulation, and fibrogenesis (Bonda et al, 2012(Bonda et al, , 2013(Bonda et al, , 2015Lau, 2011).…”

“…Immunohistochemical analysis in most cardiac tissue specimens, obtained from victims died of sudden cardiac death, revealed that CCN1 may be associated with myocardial ischemic morphology and cardiac hypertrophy, and ischemia is the possible reason for the increased expression of myocardial CCN1 protein (Hilfiker-Kleiner et al, 2004;Papetta et al, 2013). Also, in several animal experiments, it was found that CCN1 expression increased in cardiac tissue with fibrosis and cardiac-specific expression of CCN1 resulted in the reduction of cardiac fibrosis in murine models of cardiac diseases (Bonda et al, 2012(Bonda et al, , 2013(Bonda et al, , 2015Meyer et al, 2016). Furthermore, one in vitro experiment confirmed that CCN1 increased the survival of myocytes by activating the integrin β1-Akt pathway under conditions of oxidative stress, whereas knockdown of CCN1 decreased the number of surviving cells under these conditions (Yoshida et al, 2007).…”

“…There is mounting evidence that CCN1 plays critical roles in cardiovascular development, embryogenesis, wound healing, inflammation regulation, and fibrogenesis (Bonda et al, 2012, 2013, 2015; Lau, 2011). Immunohistochemical analysis in most cardiac tissue specimens, obtained from victims died of sudden cardiac death, revealed that CCN1 may be associated with myocardial ischemic morphology and cardiac hypertrophy, and ischemia is the possible reason for the increased expression of myocardial CCN1 protein (Hilfiker‐Kleiner et al, 2004; Papetta et al, 2013).…”