title: Silencing MR-1 attenuates inflammatory damage in mice heart induced by AngII.
abstract: Myofibrillogenesis regulator-1(MR-1) can aggravate cardiac hypertrophy induced by angiotensin(Ang) II in mice through activation of NF-kappaB signaling pathway, and nuclear transcription factor (NF)-kappaB and activator protein-1(AP-1) regulate inflammatory and immune responses by increasing the expression of specific inflammatory genes in various tissues including heart. Whether inhibition of MR-1 expression will attenuate AngII-induced inflammatory injury in mice heart has not been explored. Herein, we monitored the activation of NF-kappaB and AP-1, together with expression of pro-inflammatory of interleukin(IL)-6, tumor necrosis factor(TNF)-alpha, vascular-cell adhesion molecule (VCAM)-1, platelet endothelial cell adhesion molecule (PECAM), and inflammatory cell infiltration in heart of mice which are induced firstly by AngII (PBS),then received MR-1-siRNA or control-siRNA injecting. We found that the activation of NF-kappaB and AP-1 was inhibited significantly, together with the decreased expression of IL-6, TNF-alpha, VCAM-1, and PECAM in AngII-induced mice myocardium in MR-1-siRNA injection groups compared with control-siRNA injecting groups. However, the expression level of MR-1 was not an apparent change in PBS-infused groups than in unoperation groups, and MR-1-siRNA do not affect the expression of MR-1 in PBS-infused mice. Our findings suggest that silencing MR-1 protected mice myocardium against inflammatory injury induced by AngII by suppression of pro-inflammatory transcription factors NF-kappaB and AP-1 signaling pathway.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Key Lab of Antibiotic Biotechnology, Ministry of Health, Beijing 100050, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Dai
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.forename: Jiandong
authors.initials: J
authors.lastname: Jiang
authors.forename: Weijia
authors.initials: W
authors.lastname: Kong
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D055785:Gene Knockdown Techniques; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics*; D009205:Myocarditis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; C547209:myofibrillogenesis regulator-1, mouse; D000804:Angiotensin II