Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Conference Poster Year : 2021

Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear

Abstract

Muscle atrophy arises from a multiplicity of physio-pathological situations caused by an imbalance between protein synthesis and breakdown. The E3 enzymes play a predominant role in muscle proteolytic machinery by targeting contractile proteins for degradation; hence some of them are referred as atrogenes (atrophy-related genes). Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Expression of the usual atrogenes did not vary between the hibernating and the active season in bear muscle, while an upregulation was observed in the unloaded mouse muscle. Interestingly, we noted changes in expression of some E3s identified as participating in the regulation of the TGF-β superfamily, a cellular pathway divided in two canonical signaling: TGF-β and BMP signaling involved respectively in muscle mass loss and maintenance. We reported here that E3s involved in TGF-β inhibition and BMP signal transduction were up- and downregulated in the hibernating bear muscle, respectively, and the contrary was observed in the unloaded mouse muscle. Moreover, TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. Our data suggest TGF-β/BMP balance as crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy, and a potential therapeutic target could be to manipulate the expression of E3s involved in their regulation.
No file

Dates and versions

hal-04209822 , version 1 (18-09-2023)

Licence

Identifiers

  • HAL Id : hal-04209822 , version 1

Cite

Laura Cussonneau, Emeric Dubois, Jon Arnemo, Christian Boyer, Christiane Deval, et al.. Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear. 9th Proteasome and Autophagy Congress, Oct 2021, Clermont-Ferrand, France. ⟨hal-04209822⟩
36 View
0 Download

Share

More