Gene expression profiling of skeletal muscles treated with a soluble activin type IIB receptor

Inhibition of the myostatin signaling pathway is emerging as a promising therapeutic means to treat muscle wasting disorders. Activin type IIB receptor is the putative myostatin receptor, and a soluble activin receptor (ActRIIB-Fc) has been demonstrated to potently inhibit a subset of TGF-beta family members including myostatin. In order to determine reliable and valid biomarkers for myostatin pathway inhibition, we assessed gene expression profiles for quadriceps muscles from mice treated with ActRIIB-Fc compared to mice genetically lacking myostatin and control mice. RNA extracted from quadriceps muscles of four classes of two-month-old female mice were analyzed with Affymetrix microarrays: control mice, myostatin-null mice, mice treated with one dose of ActRIIB-Fc and mice treated with four doses of ActRIIB-Fc. An initial study used 3 mice from each class, and an independent follow-up study used 8 myostatin-null mice and 5 mice from each of the other 3 classes.肌抑素（myostatin）信号通路的抑制作用正逐渐成为治疗肌肉萎缩类疾病的极具潜力的治疗手段。激活素IIB型受体（Activin type IIB receptor）为推定的肌抑素受体，已有研究证实可溶性激活素受体（ActRIIB-Fc）可强效抑制包括肌抑素在内的部分转化生长因子-β（TGF-β）家族成员。为确定肌抑素通路抑制的可靠且有效的生物标志物，本研究对比分析了经ActRIIB-Fc处理的小鼠、肌抑素基因敲除小鼠与正常对照小鼠的股四头肌基因表达谱。本研究对四组2月龄雌性小鼠的股四头肌提取的RNA进行了Affymetrix基因芯片（Affymetrix microarrays）分析：四组分别为正常对照小鼠、肌抑素敲除型小鼠、单次给药ActRIIB-Fc的小鼠以及四次给药ActRIIB-Fc的小鼠。初始研究中每组纳入3只小鼠，而独立后续研究则纳入8只肌抑素敲除型小鼠，其余三组每组各纳入5只小鼠。