From quiescence to repair: C/EBPβ as a regulator of muscle stem cell function in health and disease

FEBS J. 2022 Nov;289(21):6518-6530. doi: 10.1111/febs.16307. Epub 2021 Dec 9.

Abstract

CCAAT/Enhancer Binding protein beta (C/EBPβ) is a transcriptional regulator involved in numerous physiological processes. Herein, we describe a role for C/EBPβ as a regulator of skeletal muscle stem cell function. In particular, C/EBPβ is expressed in muscle stem cells in healthy muscle where it inhibits myogenic differentiation. Downregulation of C/EBPβ expression at the protein and transcriptional level allows for differentiation. Persistence of C/EBPβ promotes stem cell self-renewal and C/EBPβ expression is required for mitotic quiescence in this cell population. As a critical regulator of skeletal muscle homeostasis, C/EBPβ expression is stimulated in pathological conditions such as cancer cachexia, which perturbs muscle regeneration and promotes myofiber atrophy in the context of systemic inflammation. C/EBPβ is also an important regulator of cytokine expression and immune response genes, a mechanism by which it can influence muscle stem cell function. In this viewpoint, we describe a role for C/EBPβ in muscle stem cells and propose a functional intersection between C/EBPβ and NF-kB action in the regulation of cancer cachexia.

Keywords: CCAAT/Enhancer Binding Protein beta; NF-kB; cancer cachexia; muscle regeneration; muscle satellite cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cachexia* / metabolism
  • Cachexia* / pathology
  • Cell Differentiation
  • Humans
  • Muscle Development / genetics
  • Muscle, Skeletal / metabolism
  • Myoblasts / metabolism
  • Neoplasms* / pathology

Substances

  • CCAAT-Enhancer-Binding Protein-beta

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