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1.
J Cell Mol Med ; 24(2): 1795-1803, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31815360

RESUMEN

Atrial fibrosis is an important factor in the initiation and maintenance of atrial fibrillation (AF); therefore, understanding the pathogenesis of atrial fibrosis may reveal promising therapeutic targets for AF. In this study, we successfully established a rapid atrial pacing canine model and found that the inducibility and duration of AF were significantly reduced by the overexpression of c-Ski, suggesting that this approach may have therapeutic effects. c-Ski was found to be down-regulated in the atrial tissues of the rapid atrial pacing canine model. We artificially up-regulated c-Ski expression with a c-Ski-overexpressing adenovirus. Haematoxylin and eosin, Masson's trichrome and picrosirius red staining showed that c-Ski overexpression alleviated atrial fibrosis. Furthermore, we found that the expression levels of collagen III and α-SMA were higher in the groups of dogs subjected to right-atrial pacing, and this increase was attenuated by c-Ski overexpression. In addition, c-Ski overexpression decreased the phosphorylation of smad2, smad3 and p38 MAPK (p38α and p38ß) as well as the expression of TGF-ß1 in atrial tissues, as shown by a comparison of the right-atrial pacing + c-Ski-overexpression group to the control group with right-atrial pacing only. These results suggest that c-Ski overexpression improves atrial remodelling in a rapid atrial pacing canine model by suppressing TGF-ß1-Smad signalling and p38 MAPK activation.


Asunto(s)
Remodelación Atrial , Estimulación Cardíaca Artificial , Atrios Cardíacos/fisiopatología , Proteínas Proto-Oncogénicas/metabolismo , Animales , Modelos Animales de Enfermedad , Perros , Fenómenos Electrofisiológicos , Matriz Extracelular/metabolismo , Fibrosis , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
2.
Int J Clin Exp Med ; 8(4): 6601-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26131291

RESUMEN

OBJECTIVE: To establish obese rat models by high-fat diet, screen microRNAs by microarray in the omental adipose tissue, and find out differential expression of microRNAs in obese rats, for further understanding the role of microRNAs as regulating molecules in obesity-induced lipid metabolism disorders. METHODS: 40 male SD rats were randomly divided into normal diet group and high-fat diet group, respectively. After fed for 8 weeks, rats were weighted, measured length and other characteristics were observed. Eye blood was taken to test blood glucose level, blood lipids level, insulin level and other indicators. The omental adipose tissue was measured by electronic analytical scales and saved at -80°C liquid nitrogen. Fat cells were stained by oil red to observe their morphology under microscopy. The expression of microRNAs was screened by microarray, and verified by Real-Time PCR. RESULTS: After high-fat diet for 4 and 8 weeks, some fatty indicators changed, including increased body weight, omental fat weight, triglycerides, total cholesterol, low-density lipoprotein, blood glucose level and insulin level, and decreased high-density lipoprotein, and differential phenotype of fat cells. Besides, by microarray techniques and Real-Time PCR, 13 differential expression microRNAs were identified, including 7 up-regulated microRNAs (microRNA30a, microRNA7e, microRNA30c, microRNA335, microRNA103, microRNA107, microRNA139-5p), and 6 down-regulated microRNAs (microRNA494, microRNA140, microRNA342-5p, microRNA382, microRNA17-1-3p, microRNA92a). CONCLUSION: Changes in the expression of microRNAs contribute to the pathogenesis of many diseases, including obesity disorders. These alterations can be due to various mechanisms, such as cell proliferation, apoptosis, migration, and differentiation, providing new therapies for diseases.

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