Altered fibrinogen level and fibrin clot structure in myostatin homozygous mutant pig

Abstract

Obesity is associated with increased serum fibrinogen level. Myostatin (MSTN), a strong inhibitor of skeletal muscle growth, is recognized as a potential target for obesity. However, the effect of MSTN inhibition on fibrinogen is not largely known. The objective of the present study was to explore fibrinogen levels after MSTN inhibition. Fibrinogen levels and the fibrin clot structure of MSTN homozygous knockout (KO) and wild‐type (WT) pigs (n = 4 in each group) were investigated. The protein expression of fibrinogen in the serum and liver of KO pigs decreased greatly (1.6‐fold loss for serum and 2.5‐fold loss for liver). KO pigs showed significantly decreased gene expression of fibrinogen chains: FGA (fibrinogen‐α; 11‐fold), FGB (fibrinogen‐β; 8‐fold) and FGG (fibrinogen‐γ; 7.4‐fold). The basal transcriptional regulators of fibrinogen, HNF1 (hepatocyte nuclear factor 1) and CEBP‐α (CCAAT/Enhancing‐binding protein‐alpha) were remarkably down‐regulated after interruption of MSTN expression by siRNA (small interfering RNA) in cultured hepatocytes (about 2‐ and 4‐fold, respectively). Compared with WT pigs, KO pigs displayed altered fibrin clot structure with thinner fibers, decreased turbidity and increased permeability. The findings indicate that the inhibition of MSTN could affect fibrinogen levels and the fibrin clot structure.

RNA sequencing analysis revealed differentially expressed genes and their functional annotation in porcine longissimus dorsi muscle affected by dietary lysine restriction

“…Six BP terms were significantly enriched under the lysine restriction status (Figure 3), of which protein polymerization (66-fold), fibrinolysis (79-fold), and plasminogen activation (99-fold) were highly enriched. Based on these terms, it can be seen that some DEGs are mostly associated with the homeostasis, wound healing, inflammation, angiogenesis, and several other biological functions (41,42). For example, fibrinogen, a proteolytic glycoprotein, composed of three closely linked polypeptides coded from FGA, FGB, and FGG genes.…”

“…For example, fibrinogen, a proteolytic glycoprotein, composed of three closely linked polypeptides coded from FGA, FGB, and FGG genes. Dietary lysine restriction downregulated these genes that may affect the rate of fibrinogen synthesis and result in abnormalities in blood circulation (42), which in turn may indirectly affect the transportation of oxygenated blood or nutrients to the muscle.…”

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

“…One of these MSTN -edited models, its progeny, or its crosses were further investigated . These include investigations on fiber-type distribution and expression of myosin heavy chain isoforms; shift from slow- to fast-twitch muscle fibers in skeletal muscle; internal organ size; semen quality and fertilization ability; reproductive trait characterization in MSTN -edited crosses; collagen-related pathological features (umbilical hernia and tippy toe standing); regulation of body fat deposition; fibrinogen levels and fibrin clot structure; esophageal striated muscle development and regulation of muscle fiber types; extraocular muscles; cardiac extracellular matrix; growth of smooth muscle in uterine horns of MSTN mutant gilts; smooth muscle content in corpus cavernosum of MSTN mutant boars; erythrocyte osmotic fragility, hematological parameters, and fatty acid composition of serum and erythrocyte membranes; miR-455-3p regulation of myoblast differentiation; composition and alteration of gut microbiota; analysis of meat and fatty acids characteristics; and development of a restriction enzyme-mediated PCR-RFLP assay for genotyping MSTN mutant pigs …”