FISH & SHELLFISH IMMUNOLOGY
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2020
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IF 0
Liting Wu,Along Gao,Yang Lei,Jun Li,Kangsen Mai,Jianmin Ye
Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1), a kind of protein tyrosine phosphatases (PTPs), is a critical regulator of antigen receptor signal transduction . Signal transduction of BCR is regulated by phosphatases in teleost as in mammals. In this study, SHP1 from Nile tilapia ( Oreochromis niloticus ) (OnSHP1) was identified and characterized, including the expression pattern against bacterial infection and regulation function in BCR signaling pathway. The open reading frame of OnSHP1 contains 1749 bp of nucleotide sequence , encoding a protein of 582 amino acids. The OnSHP1 protein was highly conversed compared to that of other species, including two amino-terminal SH2 domains at the N terminus and a PTP catalytic domain . Transcriptional expression analysis revealed that OnSHP1 was detected in all examined tissues and highly expressed in spleen . The up-regulated OnSHP1 expression was observed in peripheral blood, spleen and anterior kidney following challenge with Streptococcus agalactiae or lipopolysaccharide (LPS) in vivo , as well as that displayed in leukocytes stimulated with S. agalactiae or LPS in vitro . Further, after induction with mouse anti-tilapia IgM monoclonal antibody in vitro , OnSHP1 was significantly up-regulated in leukocytes. When spleen leukocytes treated with PTP Inhibitor II in vitro , the phosphorylation level of OnSHP1 at the phosphorylation sites (Y 535 and Y 557 ) and the cytoplasmic free Ca 2+ concentration were up-regulated significantly. Overall, the findings of this study indicate that SHP1 gets involved in host defense against bacterial infection and BCR signaling pathway in Nile tilapia .
研究领域:
免疫学
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分子生物学
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鱼类生物学
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病原-宿主互作
✓ 已验证
产品关联
DOI
PubMed
ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Xiuhua Pan,Feiyang Liu,Ruixin Kang,Zongwei Hu,Yueru Pang,Ziqi Shen,Xiawei Zhou,Jun Zhang,Qi Shen
Despite recent advances in immunotherapy, its efficacy remains constrained by the absence of immune coordination. Especially, the interplay between tumor-draining lymph nodes (TDLNs) and tumors is frequently disregarded. Here, a self-adjuvanting hydrogel capable of eliciting a powerful and sustained immune response is developed. Briefly, the engineered arabinose response bacteria (ARB) expressing IL-15 and mannose-modified hollow mesoporous Prussian blue nanoparticles (NPs) loaded with vitamin E (Man/HMPB(VE), MHV) are mixed with arabinose hydrogel (AraGel), forming the system designated as AraGel@ARB/MHV (AAM). Employing mild photothermal therapy mediated by MHV, immunogenic cell death (ICD) triggers the release of tumor-associated antigens. Subsequently, Man-modified NPs target TDLNs and release VE, which suppresses the checkpoint Src homology region 2 domain-containing phosphatase-1 (SHP1) in dendritic cells, thereby enhancing antigen presentation and T cell activation. Meanwhile, IL-15 expression of ARB(IL-15) induced by AraGel degradation enables ARB to serve as an enhanced adjuvant in a self-adjuvanting manner, working synergistically with ICD and TDLN reprogramming to promote cytotoxic T lymphocytes activation. The hydrogel system efficiently suppresses tumor growth by eliciting prolonged and powerful immunotherapy in an orchestrated manner. Overall, the self-adjuvanting hydrogel holds great potential for cancer immunotherapy.
研究领域:
癌症免疫疗法
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生物医学工程
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
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2026
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IF 4.7
Wei Ran,Ma Jian,Yu Zeyu,Zou Wei,Zhao Na
Diabetic nephropathy (DN) is the most prevalent microvascular complication of diabetes, where a hyperglycemic environment can induce chronic damage to renal vessels and parenchyma, severely endangering patients’ health. TangShenKang decoction (TSK) is a traditional Chinese medicine formula developed based on the clinical and pathological characteristics of DN. In this study, through transcriptomic data analysis of a rat DN model and a TSK intervention group, the key regulatory gene AT2R was identified. Molecular mechanisms underlying TSK’s effects on inflammation and fibrosis in DN were investigated using Western blot, quantitative polymerase chain reaction (qPCR), and immunofluorescence staining experiments, with further in vivo validation of TSK’s therapeutic effects on DN. The results showed that TSK can activate AT2R in the DN model and promote SHP1 phosphorylation, thereby inhibiting the phosphorylation of IκBα, an important protein in the NFκB signaling pathway, reducing the secretion of inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and suppressing the progression of inflammation. Meanwhile, after activating AT2R, TSK can effectively inhibit the epithelial-mesenchymal transition (EMT) process in DN, downregulate the expression of p-Smad2/3 in the TGF-β signaling axis, and decrease the expression levels of fibrosis phenotype molecules such as connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and fibronectin 1 (FN1), thereby alleviating renal fibrosis in DN. In conclusion, the therapeutic effect of TSK on DN may be mediated through the activation of the AT2R/ATIP1/SHP1 axis, which subsequently inhibits inflammation- and fibrosis-related signaling pathways.
✓ 已验证
DOI
PubMed
高影响因子
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