TY - T1的microrna的表达的组织病理学阶段LGMD2A (Calpainopathy) (P04.081) JF -神经学乔-神经病学SP - P04.081 LP - P04.081六世- 78 - 1补充非盟首页-罗萨莱斯Xiomara盟Vinod Malik盟Amita Sneh AU - Lei陈盟Janaiah哥打盟-莎拉·刘易斯盟-朱莉Gastier-Foster盟-卡洛琳Astbury AU -罗伯特Pyatt AU -莎莉尼·Reshmi AU -路易斯Rodino-Klapac AU -里德克拉克盟-杰瑞Mendell说盟Zarife Sahenk Y1 - 2012/04/25 UR - //www.ez-admanager.com/content/78/1_Supplement/P04.081.abstract N2 -目的:检查监管microrna的表达在LGMD2A肌肉的病理阶段了解疾病发病机理。背景最近的体外研究表明,CAPN3不足导致最初加速肌纤维形成了损耗的卫星细胞池。在正常肌肉,upregulation miR-1促进转型的卫星细胞分化增殖肌原性的祖细胞。设计/方法:一个完全特征LGMD2A队列(n = 45)肌肉活检(n = 39)的量化miR-1表达式(n = 12)和罗马7,卫星细胞生物标志物。结果:三组病人聚集的年龄、疾病和临床严重程度的持续时间。组1:著名的炎症(n = 8)与嗜酸性粒细胞(n = 5)。组2 (n = 8):最小的炎性浸润,同时分散纤维坏死和再生以最小的焦血管周的纤维化。3组(n = 23):人肌内膜和突出perimysial纤维化罕见坏死/再生没有炎症。连续的变化显示了年龄、症状持续时间:组1 = 13.4±7.1岁;持续时间为4.6±3.7岁;组2 = 25.9±9.1岁;持续时间为10.9±5.6岁;和组3 = 33.9±11.8岁; duration 17.6 ± 9.3 yrs. Contrary to expectations, a significant increase of Pax7-positive satellite cells was seen in all samples with the greatest increase in the fibrotic group. Findings correlated with significant reduction in miR-1 in fibrotic group compared to others.Conclusions: The histopathological analysis identified 3 distinct stages of pathological changes representing a continuum of the disease correlating with age and disease duration. Pax7-positive satellite cell number was elevated even in the advanced dystrophic stage where reduced miR-1 failed to promote transition to satellite cell differentiation. This provides a potential entrée for treatment with miR-1 overexpression to facilitate satellite cell differentiation, skeletal muscle maturation, and promotion of normal muscle growth and regeneration.Supported by: NIH NIAMS U54 AR050733-05, Jesse's Journey, and the muscular Dystrophy Association.Disclosure: Dr. Rosales has nothing to disclose. Dr. Malik has nothing to disclose. Dr. Sneh has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Kota has nothing to disclose. Dr. Lewis has nothing to disclose. Dr. Gastier-Fosteer has received personal compensation for activities with Inova Health Sciences as a participant in a discussion group. Dr. Astbury has nothing to disclose. Dr. Pyatt has nothing to disclose. Dr. Reshmi has nothing to disclose. Dr. Rodino-Klapac has nothing to disclose. Dr. Clark has nothing to disclose. Dr. Mendell has received research support from AVI BioPharmaceuticals Inc. Dr. Sahenk has nothing to disclose.Wednesday, April 25 2012, 07:30 am-12:00 pm ER -