Chronic Aryl Hydrocarbon Receptor Activity Causes Adverse Muscle Affect: Implications for Smoking-induced Muscle Impairment

Purpose: The goal of this study was to analyze the gene expression levels by RNA sequencing from the plantaris muscle of mice exposed to normal air or tobacco smoke for 16 weeks. Methods: Plantaris muscles were removed, flash frozen, and RNA was harvested using the RNeasy Tissue Mini Kit (Qiagen), according to manufacturer’s instructions. RNA was reverse transcribed to complementary DNA (Lexogen QuantSeq 3′ FWD), and sequenced on a HiSeq 4000 instrument (Illumina). Results: Gene clusters representing neurogenesis/axon development, neuronal projection/synapse, and myofibril/sarcomere/muscle differentiation were amongst the most affected by chronic tobacco smoke exposure. In addition, mitochondrial network genes and neuromuscular genes were down-regulated in smoke-exposed mice. Conclusions: Chronic tobacco smoke exposure in mice reprograms the skeletal muscle transcriptome, with a reduction in mitochondrial and neuromuscular junction genes being consistent with mitochondrial respiratory impairment and neuromuscular junction degeneration observed at whole tissue level. Plantaris muscle mRNA profiles of wild type mice exposed to tobacco smoke for 16 weeks