Temporal Dynamics of Gene and Protein Expression Follow Volumetric Muscle Loss

Here, we performed time-series analysis of transcriptomic and proteomic changes associated with VML in a mouse model, focusing on the dynamics of gene and protein expression patterns at up to three weeks after muscle injury. We identified signaling pathways associated with temporal expression patterns that fail to restore within 3 weeks after VML, including those with sustained upregulation or downregulation. Using temporal expression analysis, we identified Sp1 as a novel molecular mediator of dysregulated muscle recovery after VML as well as elucidated pro-inflammatory and extracellular matrix (ECM) remodeling pathways mediating the remodeling process. These insights pave the way for the development of new targets that promote muscle regeneration and functional recovery of traumatically injured muscle. We utilized a well-established mouse partial-thickness VML model, in which 40% of the tibialis anterior muscle in C57BL/6 (8-week-old male) mice was unilaterally excised, based on our previous work . At time points of 3, 7, 14, and 21 days after the induction of VML, the tibialis anterior muscles were explanted for RNA extraction (n=5-6 samples per time point).