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

The neonatal isoform of the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 1 (SERCA1b) is a dominant Ca²⁺ pump in the young fibers of regenerating muscle. In vivo transfection of about 1% of the fibers with SERCA1b RNAi plasmid resulted in no apparent change in the transfected fibers, but enhanced t...

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Bibliographic Details
Published in:Histochemistry and cell biology 2011, Vol.135 (1), p.11-20
Main Authors: Zádor, Ernő, Owsianik, Grzegorz, Wuytack, Frank
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Calcineurin
Cell Biology
Developmental Biology
Fiber growth
Gene Silencing
Immunoblotting
interleukin-4
Male
Muscle Fibers, Skeletal - physiology
Muscle regeneration
Muscle, Skeletal - physiology
Muscular system
Original Paper
Protein Isoforms - genetics
Rats
Rats, Wistar
Regeneration - physiology
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
Rodents
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
SERCA1b
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Summary:The neonatal isoform of the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 1 (SERCA1b) is a dominant Ca²⁺ pump in the young fibers of regenerating muscle. In vivo transfection of about 1% of the fibers with SERCA1b RNAi plasmid resulted in no apparent change in the transfected fibers, but enhanced the increase of fresh weight and fiber 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 sufficient 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 fibers. Notably, perimuscular injection of interleukin-4 (IL-4) antibody but not that of an unrelevant antibody completely abolished the growth-promoting effect of SERCA1b RNAi. This indicates that silencing SERCA1b in a few fibers stimulates the calcineurin-NFAT-IL-4 pathway and fiber growth in the whole regenerating soleus. These results suggest the presence of an autocrine-paracrine coordination of growing muscle fibers, and put forward a new method to stimulate skeletal muscle regeneration.
ISSN:0948-6143
1432-119X
DOI:10.1007/s00418-010-0766-y