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Abstract :
The Peroxisome Proliferator-Activated Receptors Beta
(PPARâ), is a transcription factor playing an important role in muscle
physiology and immunometabolism. We hypothesized that its activation with an
agonist treatment (GW0742) of mice could alter the early-phase of the muscle
regeneration process when immune cells infiltrate in injured muscle. To
investigate this, tibialis anterior of mice treated or not with GW0742
were injured with cardiotoxin, and muscle regeneration was monitored on days 4,
7, 9 and 14 post-injury. The injury induced a decrease in PPARâ and
Myostatin expression, the latter response was more pronounced in GW0742 treated
mice. We found that treatment of mice with GW0742 increases the recruitment of
macrophages (both M1 and M2) and CD3+ lymphocytes at day 4 post-damage. This
effect is accompanied by a more pronounced response of markers of proliferation
and differentiation of satellite cells and of Myostatin. Moreover, we observed
an earlier return to basal level (7 days versus 14 days). Taken together, our
results suggest that activating PPARâ pathway in skeletal muscle could be
a therapeutic strategy in the case of certain skeletal muscle diseases or
injuries.
Key-words: Muscle, injury, regeneration, PPARâ
Résumé :
Le Peroxisome Proliferator-Activated Receptors Beta
(PPARâ), un facteur de transcription, joue un rôle important dans
la physiologie du muscle et l'immuno-métabolisme. Nous avons émis
l'hypothèse que l'activation de PPARâ par un agoniste (le GW0742)
affecte les phases précoces du processus de
régénération musculaire. Pour la vérifier, les
tibialis anterior de souris traitées ou non au GW0742 sont
blessées avec de la cardiotoxine et la régénération
musculaire est évaluée aux jours 4, 7, 9 et 14 post-blessure. Nos
résultats montrent que la blessure induit une diminution de l'expression
de PPARâ et de la Myostatine, plus marquée chez les souris
traitées au GW0742. Le traitement induit une augmentation du nombre de
macrophages (de types M1 et M2) et de lymphocytes CD3+ au jour 4 post-blessure.
Ces effets sont accompagnés d'une réponse plus prononcée
de l'expression des marqueurs de prolifération et de
différenciation des cellules satellites et de la Myostatine. De plus,
nous observons un retour plus précoce à des valeurs de base (7
jours versus 14 jours). L'ensemble de nos résultats suggère que
d'activer la voie PPARâ dans le muscle squelettique pourrait être
une stratégie thérapeutique dans le cas de certaines maladies ou
blessures musculaires.
Mots clés : Muscle, blessure,
régénération, PPARâ
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