Formoterol treatment downregulates the myostatin system in skeletal muscle of cachectic tumour-bearing rats

Abstract

Cachexia is a common systemic manifestation. Additionally, myostatin is known to be a negative regulator of skeletal muscle development. The present study aimed to investigate whether formoterol down-regulates the myostatin system in skeletal muscle of tumour-bearing rats. Real-time PCR and Western blotting were used for the analysis. Results showed that rats bearing the Yoshida AH-130 ascites hepatoma, a cachexia-inducing tumour, exhibited marked muscle wasting that affected the mass of the muscles studied. The cachectic animals exhibited a significant increase in the mRNA levels of the myostatin receptor (ActIIB) in gastrocnemius muscles. Notably, the expression of the various forms of follistatin, a protein with the opposite effects to those of myostatin, was significantly reduced as a result of the implantation of the tumour. When the animals were treated with formoterol, a β-agonist with anti-cachectic potential, increases in skeletal muscle weights were observed. The β-agonist significantly increased levels of various follistatin isoforms and significantly decreased the expression levels of the myostatin receptor. In addition, formoterol treatment resulted in a significant decrease of the myostatin protein content of the gastrocnemius muscle. In conclusion, the results presented indicate that certain anabolic actions of formoterol on the skeletal muscle of cachectic animals may be mediated via the myostatin system.

Figure 1

Muscle weights in rats bearing the Yoshida AH-130 ascites hepatoma treated with formoterol. Results are the mean ± SEM for 7 animals. Muscle weights are expressed as mg/100 g of initial body weight. GSN, gastrocnemius; TIB, tibialis; EDL, extensor digitorum longus. C, control animals; T, tumour-bearing rats; F, formoterol-treated animals. Values that were found to be significantly different by the Student’s t-test from the non-tumour-bearing animal groups are indicated by ^*p<0.05, ^**p<0.01 and ^***p<0.001. Values that were found to be significantly different by the Student’s t-test from the non-treated animal groups are indicated by ^#p<0.05, ^##p<0.01 and ^###p<0.001.