FISH & SHELLFISH IMMUNOLOGY
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2019
·
IF 3.298
Limin Wu,Yongjing Li,Yufeng Xu,Lei Wang,Xiao Ma,Chuanju Dong,Xianliang Zhao,Xue Tian,Xuejun Li,Xianghui Kong
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 ( il1 β , 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.
研究领域:
水产养殖
·
免疫学
·
分子生物学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2019
·
IF 2.705
Jinyue Zhu,Weiqing Wang,Xia Wu
Hyperplasia of airway smooth muscle cells (ASMCs) is key to the progression of asthma. Isorhynchophylline (IRN) derived from Uncaria rhynchophylla can inhibit the proliferation of AMSCs. The major purpose of the current study was to assess the effect of IRN on the asthma symptoms was assessed both in vitro and in vivo, and the associated mechanism of the effect was also explored by focusing on the function of miR-200a. Asthma model was induced using ovalbumin (OVA) method and AMSC hyperplasia model was induced using TGF-β1. The effect of IRN on allergic asthma mice and the effect of IRN on the proliferation of ASMCs were investigated as well, and the changes in miR-200a level and FOXC1/NF-κB pathway were detected. The administration of IRN attenuated the eosinophils recruitment in BALF, reduced collagen deposition in lung tissues, and suppressed production of IgE and pro-inflammation cytokines. IRN also inhibited the proliferation and induced the apoptosis of ASMCs. Moreover, the administration of IRN increased the level of miR-200a while inhibited the activation of FOXC1/NF-κB pathway. However, after the inhibition of miR-200a level, the function of IRN on ASMCs was impaired. Collectively, it was demonstrated that the effect of IRN on asthma relied on the up-regulation of miR-200a, which then deactivated FOXC1/NF-κB pathway.
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PubMed
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Experimental and Therapeutic Medicine
·
2018
·Vol. 17
·期 1
·251-259
·
IF 1.41
Meng Wang,Hui Li,Yaxin Zhao,Chuanfeng Lv,Guanghua Zhou
Rhynchophylline (Rhy) is a major active component of Uncaria rhynchophylla and exhibits the potential to inhibit the proliferation of airway smooth muscle cells (ASMCs). In the current study, it was hypothesized that Rhy serves a key role in the anti‑asthma effect of Uncaria rhynchophylla by inhibiting transforming growth factor‑β1 (TGF‑β1)‑mediated activation of Smad and mitogen‑activated protein kinase (MAPK) signaling. Allergic asthma was induced in mice using ovalbumin (OVA), and the effect of Rhy treatment on inflammatory and allergic responses in the bronchoalveolar lavage fluid (BALF) and serum of mice was determined. Subsequently, the changes in TGF‑β1‑induced Smad and MAPK signaling following Rhy administration were detected to determine the mechanism associated with this treatment. In addition, TGF‑β1 was employed to induce hyperplasia of ASMCs, and the effect of Rhy on proliferation of ASMCs, and Smad and MAPK signaling in vitro was also assessed. The administration of Rhy attenuated the recruitment of eosinophils in BALF induced by OVA, which was associated with the suppressed production of immunoglobulin E, interleukin (IL)‑13, IL‑4 and IL‑5. At the molecular level, the administration of Rhy suppressed the expression levels of TGF‑β1, Smad4, p‑Smad2 and p‑Smad3, while it induced the expression of Smad7, indicating the inhibitory effect of Rhy on TGF‑β1‑mediated Smad and MAPK signaling. Furthermore, Rhy inhibited the proliferation of ASMCs and, similar to the results of the in vivo assay, it blocked the pro‑hyperplasia signaling transduction in vitro. In conclusion, the current study demonstrated the anti‑asthma effect of Rhy, which depended on the inhibition of TGF‑β1‑mediated Smad and MAPK signaling.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Huan Chen,Jin Liu,Jia Zhang,Yuqian Chen,Yan Wang,Yuanjie Qiu,Huizhong Hu,Limin Chai,Qianqian Zhang,Qingting Wang,Manxiang Li
Bromodomain-containing protein 4 (BRD4) is recognized as a member of the bromodomain and extraterminal (BET) family that is involved in the airway inflammation and airway remodeling of asthma. However, the underlying mechanisms of BRD4 in airway smooth muscle cells (ASMCs) proliferation and airway remodeling remain unclear. Primary cultured rat ASMCs and ovalbumin (OVA)-induced rat asthma models were applied to address these issues in the present study. We showed that transforming growth factor β1 (TGF-β1) increased the protein expression of ubiquitin specific peptidase 22 (USP22), which deubiquitinated BRD4 therefore increased its expression, and then resulted in the upregulation of glioma-associated oncogene homolog 1 (GLI1) and osteopontin (OPN) leading to ASMCs proliferation. We further confirmed that induction of TGF-β1 sequentially upregulated USP22, BRD4, GLI1 and OPN leading to airway remodeling in OVA-induced rat asthma models, targeting TGF-β1/USP22/BRD4/GLI1/OPN pathway axis effectively attenuated airway remodeling and asthma development. Our study provides novel sights to understand the role of TGF-β1/USP22/BRD4/GLI1/OPN axis in airway remodeling, and targeting this pathway might have potential value for the prevention and treatment of asthma.
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高影响因子
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