Silencing SERCA1b in a few fibers stimulates growth in the entire regenerating soleus muscle

Zádor, Ernő and Owsianik, Grzegorz and Wuytack, Frank (2011) Silencing SERCA1b in a few fibers stimulates growth in the entire regenerating soleus muscle. HISTOCHEMISTRY AND CELL BIOLOGY, 135 (1). pp. 11-20. ISSN 0948-6143

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Abstract

The neonatal isoform of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 1 (SERCA1b) is a dominant Ca2+ pump in the young Wbers of regenerating muscle. In vivo transfection of about 1% of the Wbers with SERCA1b RNAi plasmid resulted in no apparent change in the transfected Wbers, but enhanced the increase of fresh weight and Wber size in the whole regenerating rat soleus muscle, until the normal size was reached. Co-transfection of calcineurin inhibitor cain/cabin-1 with SERCA1b RNAi was suYcient to cut down the widespread growth stimulation, but the subsequent transfection of cain into the SERCA1b RNAi transfected muscle did not inhibit muscle growth. The SERCA1b RNAi preferably upregulated the expression of the NFAT reporter lacZ compared to controls when co-transfected into the Wbers. Notably, perimuscular injection of interleukin-4 (IL-4) antibody but not that of an unrelevant antibody completely abolished the growth-promoting eVect of SERCA1b RNAi. This indicates that silencing SERCA1b in a few Wbers stimulates the calcineurin- NFAT-IL-4 pathway and Wber growth in the whole regenerating soleus. These results suggest the presence of an autocrine–paracrine coordination of growing muscle Wbers, and put forward a new method to stimulate skeletal muscle regeneration.

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