Exercise Altered the Skeletal Muscle MicroRNAs and Gene Expression Profiles in Burn Rats With Hindlimb Unloading

Abstract

Objective This study investigated microRNA and target gene profiles under different conditions of burn, bed rest, and exercise training. Methods Male Sprague-Dawley rats (n = 48) were assigned to sham ambulatory, sham hindlimb unloading, burn ambulatory, or burn plus hindlimb unloading groups. Rats received a 40% total body surface area scald burn or sham treatments and were ambulatory or hindlimb unloaded. Rats were further assigned to exercise or no exercise. Plantaris tissues were harvested on day 14 and pooled to analyze for microRNA and gene expression profiles. Results Compared to the sham ambulatory-no exercise group, 73, 79, and 80 microRNAs were altered two-fold in the burn ambulatory, sham hindlimb unloading, and burn hindlimb unloading groups, all with no exercise, respectively. Over 70% of microRNAs were upregulated in response to burn and hindlimb unloading, while 60% microRNA of the profile decreased in hindlimb unloaded burn rats with exercise training. MiR-182 was the most affected in rat muscle. GO biological process and pathway analysis showed that the oxidative stress pathway was most stimulated in the hindlimb unloaded burn rats; while in response to exercise training, all genes in related pathways such as hypermetabolic, inflammation and blood coagulation were alleviated. Conclusions MicroRNAs and transcript gene profiles were altered in burn and hindlimb unloading groups, with additive effects on hindlimb unloaded burn rats. The altered genes' signal pathways were associated with muscle mass loss and function impairment. Muscle improvement with exercise training was observed in gene levels with microRNA alterations as well.

Burn Serum Stimulates Myoblast Cell Death Associated with IL-6-Induced Mitochondrial Fragmentation

“…The possible pathway involved an miRNA 140-negative interaction with Mfn1 in cardiomyocyte apoptosis (36). Our previously published study showed that miR-140–3p related to mitochondrial dynamics regulation increased 1.17 fold in plantaris muscle from 40% TBSA burn rats 14 days later (37). …”

Severe Burn-Induced Inflammation and Remodeling of Achilles Tendon in a Rat Model

“…Considering the tendon as the connector and force transmitter between skeletal muscle and bone, it is essential to understand tendon's behavior in response to severe injury. Future investigation regarding the modulation of the inflammatory cascade and MMP inhibition accompanied by regulated physical therapy that allows proper tissue loading to prevent disuse, but also prevent overuse ( 31 – 35 ) may be promising for the improvement of recovery after severe burn and other traumatic injuries.…”

Muscle unloading: A comparison between spaceflight and ground‐based models

“…The loss of muscle force‐generating capacity associated with mechanical unloading is well established (Table ). Thus, numerous studies show that HU results in a reduced force‐generating capacity of the hindlimb muscles in rats and mice . Muscle weakness is partly because of reduced muscle mass but defect in the intrinsic force‐generating capacity of skeletal muscle also contributes.…”

“…Thus, numerous studies show that HU results in a reduced force-generating capacity of the hindlimb muscles in rats and mice. [56][57][58][59][60] Muscle weakness is partly because of reduced muscle mass but defect in the intrinsic force-generating capacity of skeletal muscle also contributes. These findings are translated to single muscle fibres, which show reduction in the force/cross-sectional area (specific force) during muscle unloading.…”