Evidence of myomiR regulation of the pentose phosphate pathway during mechanical load-induced hypertrophy

Taylor Valentino, Vandre C. Figueiredo, C. Brooks Mobley, John J. McCarthy, Ivan J. Vechetti

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Article numbere15137
JournalPhysiological Reports
Volume9
Issue number23
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This work was supported by funding from the NIH National Institute of General Medical Sciences (grant no. P20GM104320‐07) to IJV.

Publisher Copyright:
© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Keywords

  • NADPH
  • myomiR
  • pentose phosphate pathway
  • redox metabolism
  • skeletal muscle hypertrophy

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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