Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration

Xiaoling Liu, Er Zu, Xinyu Chang, Xiaowei Ma, Ziqi Wang, Xintong Song, Xiangru Li, Qing Yu, Ken Ichiro Kamei, Toshihiko Hayashi, Kazunori Mizuno, Shunji Hattori, Hitomi Fujisaki, Takashi Ikejima, Dan Ohtan Wang

Research output: Contribution to journalArticlepeer-review


Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling, including an acute and transient breakdown of collagen that produces gelatin. Although the physiological function of this process is unclear, it has inspired the application of gelatin to injured skeletal muscle for a potential pro-regenerative effect. Here, we investigated a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by the hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulated ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulated the antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggered the release of the myokine IL-6, which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulated ROS overproduction from NOX2 and the mitochondrial chain complex, and ROS accumulation by suppressing the antioxidant system, triggering the release of TNFα, which inhibits myogenesis and regeneration. Our results have revealed a bi-phasic role of gelatin in regulating skeletal muscle repair mediated by intracellular ROS, the antioxidant system and cytokine (IL-6 and TNFα) signaling.

Original languageEnglish (US)
Article numberdmm049290
JournalDMM Disease Models and Mechanisms
Issue number12
StatePublished - Dec 2021


  • Gelatin
  • Hormesis
  • IL-6/TNFα
  • NOX2
  • ROS
  • Skeletal muscle regeneration

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology


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