Aldosterone stimulation of fibroblasts affects gene expression and function relevant to muscle injury and disease

Here, we report the RNA sequencing of fibroblasts isolated from wild-type (C57BL/10) neonatal hindlimb skeletal muscle. The fibroblasts were directly treated with the MR agonist aldosterone, the MR antagonist spironolactone, or vehicle control (DMSO). We find that aldosterone treatment increased expression of genes involved in fibrosis, muscle function, and metabolism, and that aldosterone treatment decreased expression of genes involved in cell migration and cytokine receptor binding. This data suggests that MR signaling can directly affect fibroblasts and contribute to pathology in skeletal muscle. Overall design: RNA-seq profiling of wild-type (C57/BL 10) neonatal mouse hindlimb skeletal muscle fibroblasts, treated for 48h with either 1 uM aldosterone, 1 uM spironolactone, or vehicle control (DMSO).

本研究针对从野生型（wild-type）C57BL/10新生小鼠后肢骨骼肌中分离的成纤维细胞（fibroblasts）开展RNA测序（RNA sequencing）。将该成纤维细胞分别以盐皮质激素受体（mineralocorticoid receptor, MR）激动剂醛固酮（aldosterone）、MR拮抗剂螺内酯（spironolactone）或溶剂对照（DMSO，二甲基亚砜）进行直接处理。研究发现，醛固酮处理可上调参与纤维化（fibrosis）、肌肉功能及代谢过程的基因表达，同时下调参与细胞迁移与细胞因子受体结合的基因表达。该数据表明，MR信号转导可直接作用于成纤维细胞，并参与骨骼肌病理进程的发生发展。
实验设计概述：对野生型（C57/BL 10）新生小鼠后肢骨骼肌成纤维细胞进行RNA-seq表达谱分析，分别以1 μM醛固酮、1 μM螺内酯或溶剂对照（DMSO）处理48小时。