Engineering Lab of Henan Province for Aquatic Animal Disease Control, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; College of Life Science, Henan Normal University, Xinxiang, 453007, PR China.
Engineering Lab of Henan Province for Aquatic Animal Disease Control, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China.
Fish Shellfish Immunol. 2020 Mar;98:710-719. doi: 10.1016/j.fsi.2019.11.015. Epub 2019 Nov 7.
Myostatin, through type I receptor (kinase 4, 5, ALK4/5), functions to participate in the immune system and negatively regulate muscle growth in mammals. However, the role of myostatin (mstn) in the immune system of teleosts is largely unknown. In a previous study, we cloned the mstn1 cDNA encoding myostatin in Qi river crucian carp (Carassius auratus). In the present study, we have cloned mstn2 cDNA, which was characterized and analyzed together with mstn1. Tissue distribution analysis showed that both mstn genes are expressed in numerous tissues, with mstn1 dominantly expressed in the muscle and brain, whereas mstn2 is mainly expressed in the brain. During embryogenesis, mstn1 and mstn2 exhibit different expression patterns. Both mstn1 and mstn2 expression increased stepwise in the brain at different developmental stages. Furthermore, both genes are differentially regulated during different periods of fasting/re-feeding. Following the exposure of C. auratus to polyI:C, lipopolysaccharide (LPS), and Aeromonas hydrophila, both genes were upregulated in different tissues, which indicated that they might be involved in the immune response against pathogenic invasion. Blocking the Mstn signal pathway with SB-431542 (a chemical inhibitor of ALK4/5) resulted in significantly increased body length and weight. However, the mortality of SB-431542-treated fish was higher after A. hydrophila challenge. Moreover, decreased expression of lysozymes (lyz), complement component 3 (c3), β-defensin 3 (defb3), and interferon γ (ifnγ) were exhibited in treated fish, compared with the controls. Furthermore, the expression of nf-κb1, three pro-inflammatory cytokines (il1β, il6, and tnfα), and inflammatory cytokines (il8 and il10) were significantly increased in both the SB-431542-treated group and the control after A. hydrophila infection, suggesting that the NF-κB pathway was not suppressed in the SB-431542-treated fish. Taken together, our data suggest that both mstn1 and mstn2 play important roles in early body development, muscle growth, and the immune system by acting downstream of the NF-κB signal pathway.
肌肉生长抑制素（Myostatin，MSTN）通过 I 型受体（激酶 4、5、ALK4/5）发挥作用，参与免疫系统，并负向调节哺乳动物的肌肉生长。然而，肌肉生长抑制素（MSTN）在鱼类免疫系统中的作用在很大程度上尚不清楚。在之前的研究中，我们克隆了淇河鲫（Carassius auratus）中的 MSTN1 cDNA，该基因编码肌肉生长抑制素。在本研究中，我们克隆了 MSTN2 cDNA，并对其进行了特征分析，同时还分析了 MSTN1。组织分布分析表明，这两个基因都在许多组织中表达，MSTN1 在肌肉和大脑中表达占优势，而 MSTN2 主要在大脑中表达。在胚胎发育过程中，MSTN1 和 MSTN2 表现出不同的表达模式。在不同的发育阶段，MSTN1 和 MSTN2 在大脑中的表达都呈逐步增加的趋势。此外，在不同的禁食/再投喂期间，这两个基因的表达都有差异。在淇河鲫暴露于聚肌胞、脂多糖（LPS）和嗜水气单胞菌后，这两个基因在不同组织中均上调，这表明它们可能参与了对病原体入侵的免疫反应。用 SB-431542（ALK4/5 的化学抑制剂）阻断 MSTN 信号通路会导致鱼体长度和体重显著增加。然而，在受到嗜水气单胞菌攻击后，接受 SB-431542 治疗的鱼的死亡率更高。此外，与对照组相比，接受 SB-431542 治疗的鱼的溶菌酶（lyz）、补体成分 3（c3）、β-防御素 3（defb3）和干扰素γ（ifnγ）的表达水平降低。此外，在 SB-431542 处理组和对照组感染嗜水气单胞菌后，nf-κb1、三种促炎细胞因子（il1β、il6 和 tnfα）和炎症细胞因子（il8 和 il10）的表达均显著增加，表明 NF-κB 信号通路在 SB-431542 处理的鱼中没有受到抑制。综上所述，我们的数据表明，MSTN1 和 MSTN2 都通过 NF-κB 信号通路发挥作用，在早期身体发育、肌肉生长和免疫系统中发挥重要作用。
