Kinetics of changes in gene and microRNA expression related with muscle inflammation and protein degradation following LPS-challenge in weaned piglets

Abstract

To test the dynamic changes of the expression of genes and microRNA in the gastrocnemius muscle after LPS challenge, 36 piglets were assigned to a control group (slaughtered 0 h after saline injection) and LPS groups (slaughtered at 1 h, 2 h, 4 h, 8 h, and 12 h after LPS treatment, respectively). After LPS treatment, the mRNA expression of IL-1β, IL-6, and TNF-α reached maximal levels at 1 h, 2 h, and 1 h, respectively ( P < 0.05), and mRNA expression of TLR4, NODs, muscle-specific ring finger 1, and muscle atrophy F-box peaked at 12 h ( P < 0.05). Moreover, the expression of miR-122, miR-135a, and miR-370 reduced at 1 h, 1 h, and 2 h, respectively ( P < 0.05), and miR-34a, miR-224, miR-132, and miR-145 reached maximum expression levels at 1 h, 1 h, 2 h, and 4 h, respectively ( P < 0.05). These results suggested that mRNA expression of pro-inflammatory cytokines was elevated in the early stage, mRNA expression of genes related to TLR4 and NODs signaling pathways and protein degradation increased in the later phase, and the expression of microRNA related to muscle inflammation and protein degradation changed in the early stage after LPS injection.

Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge

“…Studies have shown that G. parasuis can adhere to and invade different types of epithelial/endothelial cells including PUVEC [47], AOC-45 [48], PBMEC [49], PK-15 [50], NPTr, and SJPL [51], implying a capability of the bacteria to invade the bloodstream for replications and cause severe inflammation in the infected organs. Inflammation often leads to skeletal muscle atrophy [11,52], consistent with the common observation that the body tends to lose weight under pathological or physiological stress.…”

“…In this study, several metabolism-related processes and pathways were significantly enriched, reflecting metabolic disorders in piglets after G. parasuis infection. Along with the inflammatory response in skeletal muscle, these stress conditions likely trigger the activation of the FoxO pathway and dysregulated miRNA expression [ 52 ]. Previous evidence has shown that activated FoxO signaling pathway and upregulated FOXO1/2/3 can cause skeletal muscle atrophy [ 54 , 55 ].…”

“…Importantly, FOXO1 , FOXO4 , FBXO32 , and TRIM63 were all targeted by downregulated miR-370 with absolutely opposite expression patterns in our results. Regarding miR-370, its downregulation in weaned piglets with acute inflammation induced by LPS, with the upregulation of FOXO1 , FOXO4 , FBXO32 , and TRIM63 in the gastrocnemius muscle [ 52 ]. In mice, miR-370-3p has been shown to directly inhibit the differentiation of C2C12 myoblasts [ 69 ].…”