Oliveira Thamires Siqueira de, Shimabukuro Marilia Kimie, Monteiro Victoria Regina Siqueira, Andrade Cherley Borba Vieira, Boelen Anita, Wajner Simone Magagnin, Maia Ana Luiza, Ortiga-Carvalho Tania Maria, Bloise Flavia Fonseca
Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Department of Histology and Embryology, Roberto Alcantara Gomes Institute of Biology, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20551-030, Brazil.
Metabolites. 2022 May 6;12(5):416. doi: 10.3390/metabo12050416.
Thyroid hormone (TH) signaling controls muscle progenitor cells differentiation. However, inflammation can alter muscle TH signaling by modulating the expression of TH transporters (, receptors (), and deiodinase enzymes ( and ). Thus, a proinflammatory environment could affect myogenesis. The role of a low-grade inflammatory milieu in TH signaling during myogenesis needs further investigation. Herein, we aimed to study the impact of the bacterial lipopolysaccharide (LPS)-induced inflammatory stimulus on the TH signaling during myogenesis. C2C12 myoblasts differentiation was induced without (CTR) or with 10 ng/mL LPS presence. The myoblasts under LPS stimulus release the proinflammatory cytokines (IL-6 and IL-1β) and chemokines (CCL2 and CXCL-1). LPS decreases expression by 28% during the initial myogenesis, thus reducing the myogenic stimulus. At the same time, LPS reduced the expression of by 41% but doubled the D2 enzymatic activity. The late differentiation was not affected by inflammatory milieu, which only increased the gene expression by 38%. LPS altered the intracellular metabolism of TH and reduced the initial myogenic stimulus. However, it did not affect late differentiation. Increased intracellular TH activation may be the compensatory pathway involved in the recovery of myogenic differentiation under a low-grade inflammatory milieu.
甲状腺激素（TH）信号传导控制肌肉祖细胞的分化。然而，炎症可通过调节TH转运体（ ）、受体（ ）和脱碘酶（ 和 ）的表达来改变肌肉TH信号传导。因此，促炎环境可能会影响肌生成。低度炎症环境在肌生成过程中对TH信号传导的作用尚需进一步研究。在此，我们旨在研究细菌脂多糖（LPS）诱导的炎症刺激对肌生成过程中TH信号传导的影响。在无（对照）或存在10 ng/mL LPS的情况下诱导C2C12成肌细胞分化。LPS刺激下的成肌细胞释放促炎细胞因子（IL-6和IL-1β）和趋化因子（CCL2和CXCL-1）。在初始肌生成过程中，LPS使 表达降低28%，从而减少肌源性刺激。同时，LPS使 的表达降低41%，但使D2酶活性增加一倍。晚期分化不受炎症环境影响，炎症环境仅使 基因表达增加38%。LPS改变了TH的细胞内代谢并减少了初始肌源性刺激。然而，它并未影响晚期分化。细胞内TH激活增加可能是低度炎症环境下参与肌源性分化恢复的代偿途径。
