Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Novel Growth Network in Muscle Regeneration is Revealed by Molecular Acupuncture-like In Vivo Transfection

Version 1 : Received: 22 February 2024 / Approved: 26 February 2024 / Online: 26 February 2024 (11:54:10 CET)

A peer-reviewed article of this Preprint also exists.

Zádor, E. Characterization of Skeletal Muscle Regeneration Revealed a Novel Growth Network Induced by Molecular Acupuncture-like Transfection. Biomolecules 2024, 14, 363. Zádor, E. Characterization of Skeletal Muscle Regeneration Revealed a Novel Growth Network Induced by Molecular Acupuncture-like Transfection. Biomolecules 2024, 14, 363.

Abstract

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

Keywords

skeletal muscle; regeneration; molecular acupuncture; SERCA; Ras; in vivo transfection

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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