Neuregulin-1β modulates myogenesis in septic mouse serum-treated C2C12 myotubes in vitro through PPARγ/NF-κB signaling
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Sepsis-induced skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass. Cytokine-induced apoptosis and impaired myogenesis play key roles in the development of this condition. However, the complete underlying mechanism remains largely unknown. Neuregulins are glial growth factors essential for myogenesis that regulate muscle metabolism. We investigated the role of neuregulin-1β (NRG-1β) in sepsis-induced apoptosis and myogenesis in skeletal muscle using a serum-based in vitro sepsis model. C2C12 myoblasts were differentiated by treatment with proliferative medium for 7 days. Then, cells were treated with 2% sham mouse serum, 1 nM NRG-1β in 2% sham mouse serum, 2% septic mouse serum (SMS), or 1 nM NRG-1β in 2% SMS. Exposure to SMS induced apoptosis, impaired myogenesis, and downregulated PPARγ. NRG-1β co-incubation remedied all these effects and inhibited NF-κB transcriptional activity. A specific PPARγ antagonist (GW9662) was also administered as a 2-h pretreatment to block PPARγ-mediated signaling and appeared to attenuate the effects of NRG-1β. Taken together, our results demonstrate that NRG-1β functions via a PPARγ/NF-κB-dependent pathway to modulate myogenesis and protect against apoptosis in SMS-treated C2C12 myotubes.
KeywordsNeuregulin-1 Muscular atrophy Sepsis Apoptosis PPAR gamma NF-kappa B
This work was supported by the National Natural Science Foundation of China [Grant Number 81401632]. The funding source has no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
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Conflict of interest
The authors declare that they have no conflict of interest.
Research involving Human Participants and/or Animals
All experimental procedures involving animals were approved by the Animal Ethics and Use Committee of Southwest Medical University. Male and female C57BL/6 mice were obtained from the Experimental Animal Centre of Southwest Medical University (Luzhou, China) and received humane care according to the Care and Use Committee of Southwest Medical University.
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