Volume 597, Issue 20 p. 5109-5124
Research Paper
Free to Read

Factors secreted from high glucose treated endothelial cells impair expansion and differentiation of human skeletal muscle satellite cells

Christopher K. Kargl

Christopher K. Kargl

Department of Health and Kinesiology, Purdue University

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Yaohui Nie

Yaohui Nie

Department of Health and Kinesiology, Purdue University

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Sheelagh Evans

Sheelagh Evans

Department of Health and Kinesiology, Purdue University

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Julianne Stout

Julianne Stout

Indiana University School of Medicine-West Lafayette

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Jonathan H. Shannahan

Jonathan H. Shannahan

School of Health Sciences, Purdue University

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Shihuan Kuang

Shihuan Kuang

Department of Animal Sciences, Purdue University, West Lafayette, IN, USA

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Timothy P. Gavin

Corresponding Author

Timothy P. Gavin

Department of Health and Kinesiology, Purdue University

Corresponding author T. P Gavin: Department of Health and Kinesiology, 800 W Stadium Ave, Purdue University, West Lafayette, IN 47906, USA. E-mail: [email protected]Search for more papers by this author
First published: 31 August 2019
Citations: 22

Edited by: Scott Powers & Russell Hepple

This is an Editor's Choice article from the 15 October 2019 issue.

Linked articles: This article is highlighted in a Journal Club article by Hinkley. To read this article, visit https://doi.org/10.1113/JP279038. This article is also highlighted in a Journal Club article by Casso & Brunt. To read this article, visit https://doi.org/10.1113/JP279117.

Abstract

Key points

  • Cellular communication occurs between endothelial cells and skeletal muscle satellite cells and is mitogenic for both cell types under normal conditions.
  • Skeletal muscle atrophy and endothelial cell dysfunction occur in tandem in cardiovascular disease, type II diabetes and ageing.
  • The present study investigated how induction of endothelial cell dysfunction via high glucose treatment impacts growth and differentiation of human skeletal muscle satellite cells in vitro.
  • Secreted factors from high glucose treated endothelial cells impaired satellite cell expansion and differentiation via decreased proliferation and dysregulation of p38 mitogen-activated protein kinase in satellite cells committed to myogenesis.
  • These findings highlight a novel potential role for endothelial cells in the development and pathology of skeletal muscle atrophy, which is common in patients with endothelial dysfunction related pathologies.

Cross-talk between endothelial cells (ECs) and skeletal muscle satellite cells (MuSC) has been identified as an important regulator of cellular functions in both cell types. In healthy conditions, EC secreted factors promote MuSC growth and differentiation. Endothelial and satellite cell dysfunction occur in tandem in many disease states; however, no data exist examining the impact of dysfunctional EC signalling on satellite cells. Therefore, the present study aimed to evaluate the effect that factors secreted from high glucose (HG) treated ECs have on the growth and differentiation of human satellite cells (HMuSC) using a conditioned medium (CM) cell culture model. Satellite cells were isolated from human skeletal muscle and grown in CM from normal or HG treated human umbilical vein ECs (HUVECs). Satellite cells grown in CM from HG treated HUVECs reduced growth (25%), differentiation (25%) and myonuclear fusion (35%). These responses were associated with increased superoxide (50%) and inflammatory cytokines (25–50%) in HG treated HUVECs and HG-CM. Decreased expansion of HG-CM treated HMuSCs was driven by a decrease in proliferation. Impaired gene expression and protein content of myogenic differentiation factors were preceded by decreased phosphorylation of p38 mitogen-activated protein kinase in HMuSC treated with CM from HG treated HUVECs. The results obtained in the present study are the first to show that factors secreted from HG treated ECs cause impairments in human muscle satellite cell growth and differentiation in vitro, highlighting endothelial cell health and secretion as a potential target for treating vascular disease-associated skeletal muscle dysfunction.