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J Cell Physiol ; 234(8): 13252-13262, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30580435


Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR-29a, in which it has a cardioprotective function in isoproterenol hydrochloride-induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR-29a reduces the isoproterenol hydrochloride-induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR-29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.

Fator Natriurético Atrial/metabolismo , Cardiomegalia/metabolismo , Regulação da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Regulação para Baixo , Camundongos , Camundongos Endogâmicos ICR , Miócitos Cardíacos/metabolismo
Can J Neurol Sci ; 35(4): 441-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18973060


BACKGROUND: Up to now, many "immunoactive" brain areas have been identified, such as hypothalamic nuclei, brain reward system; but the nucleus ambiguous (Amb), a nucleus nervi vagis of medulla oblongata, was less well studied in neuroimmunomodulation. METHODS: In order to obtain more profound comprehension and more knowledge on Amb, we studied the effect of acute electrical stimulation of Amb on thymus and spleen activity in rat. A stimulator was applied to stimulate the Amb of the anaesthetic rats using the parameter at 100 microgA x 5 ms x 100 Hz every 1 s for 1 min. The levels of TGF-13 and thymosin-beta4 mRNA in thymus, the release of IL-2 and IL-6 at splenocyte in vitro and splenic lymphocyte proliferation were measured at hour 0.5, 1, 2, 3 following the electrical stimulation. RESULTS: The results showed that concanavalin A (Con A)-induced splenic lymphocyte proliferation and the release of IL-2 and IL-6 were all significantly enhanced at 0.5, 1, and 2 h following effective Amb stimulation as compared to in the control group. However, as compared to in the control group, the levels of TGF-beta and thymosin-beta4 mRNA in the thymus were both remarkably reduced at 0.5, 1, and 2 h following effective Amb stimulation. CONCLUSIONS: These findings reveal that the Amb participates in the modulation of animal immune functions.

Sistema Imunitário/fisiologia , Bulbo , Baço/metabolismo , Timo/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Concanavalina A/farmacologia , Estimulação Elétrica , Feminino , Interleucina-2/imunologia , Interleucina-6/imunologia , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Bulbo/anatomia & histologia , Bulbo/metabolismo , Mitógenos/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Baço/citologia , Timosina/genética , Timosina/metabolismo , Timo/citologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo