Evidence of myomiR regulation of the pentose phosphate pathway during mechanical load‐induced hypertrophy. Issue 23 (9th December 2021)

• Record Type: Journal Article
• Authors: Valentino, Taylor; Figueiredo, Vandre C.; Mobley, C. Brooks; McCarthy, John J.; Vechetti, Ivan J.
• Is Part Of: Physiological reports. Volume 9:Issue 23(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-09
• Subjects: myomiR -- NADPH -- pentose phosphate pathway -- redox metabolism -- skeletal muscle hypertrophy; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.15137
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Many of the molecular and cellular mechanisms discovered to regulate skeletal muscle hypertrophy were first identified using the rodent synergist ablation model. This model reveals the intrinsic capability and necessary pathways of skeletal muscle growth in response to mechanical overload (MOV). Reminiscent of the rapid cellular growth observed with cancer, we hypothesized that in response to MOV, skeletal muscle would undergo metabolic programming to sustain increased demands to support hypertrophy. To test this hypothesis, we analyzed the gene expression of specific metabolic pathways taken from transcriptomic microarray data of a MOV time course. We found an upregulation of genes involved in the oxidative branch of the pentose phosphate pathways (PPP) and mitochondrial branch of the folate cycle suggesting an increase in the production of NADPH. In addition, we sought to determine the potential role of skeletal muscle‐enriched microRNA (myomiRs) and satellite cells in the regulation of the metabolic pathways that changed during MOV. We observed an inverse pattern in gene expression between muscle‐enriched myomiR‐1 and its known target gene glucose‐6‐phosphate dehydrogenase, G6pdx, suggesting myomiR regulation of PPP activation in response to MOV. Satellite cell fusion had a significant but modest impact on PPP gene expression. These transcriptomic findings suggest the robust muscle hypertrophy induced by MOV requires enhanced redox metabolism via PPP production of NADPH which is potentially regulated by a myomiR network. Abstract : During rest, myomiR‐1 levels are high resulting in the repression of Glucose‐6‐Phosphate Dehydrogenase (G6pdx). Mechanical overload (MOV) results in the decrease of myomiR‐1, and enhanced levels of G6pdx causing an increase in the activation of the pentose phosphate pathways (PPP). Delivery of a satellite cell‐enriched miR‐206 upon fusion of satellite cells at the late phase of MOV, targets G6pdx. In the absences of satellite cell fusion, G6pdx levels remain higher resulting in sustained activation of the PPP.