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TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway
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作者 Jia SONG Dong-lei SUN +8 位作者 Chen-yang LI Yu-xin LUO Qian LIU Yue YAO Hong ZHANG Ting-ting YANG Mei SONG Xin-li BAI Xiao-lan ZHANG 《Current Medical Science》 SCIE CAS 2024年第3期519-528,共10页
Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium ... Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis model.This study aimed to explore the effects of TL1A on human colonic fibroblasts.Methods A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis.The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)supernatant.The proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western blotting.Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group.Transforming growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group.The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 h.TL1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co cells.Treatment of CCD-18Co cells with TL1A increased the expression of TGF-β1 and p-Smad3.Conclusion TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway. 展开更多
关键词 tumor necrosis factor ligand-related molecule-1a fibrosis inflammatory bowel disease MYOFIBROBLASTS transforming growth factor1
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Protective Effect and Mechanism of Sodium Tanshinone ⅡA Sulfonate on Microcirculatory Disturbance of Small Intestine in Rats with Sepsis 被引量:9
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作者 祝伟 吕青 +2 位作者 陈华文 王照华 钟强 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2011年第4期441-445,共5页
To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal l... To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture(CLP).Rats were randomly divided into 3 groups:sham operated group(S),sepsis group(CLP) and STS treatment group(STS).STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay(ELISA).The expression of intercellular adhesion molecule-1(ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB(NF-κB) and tissue factor(TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP(P0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α(P0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality. 展开更多
关键词 sodium tanshinone ⅡA sulfonate SEPSIS nuclear factor κB tumor necrosis factor intercellular adhesion molecule-1 tissue factor
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Early detection of hepatocellular carcinoma co-occurring with hepatitis C virus infection: A mathematical model 被引量:2
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作者 Abdel-Rahman Nabawy Zekri Amira Salah El-Din Youssef +6 位作者 Yasser Mabrouk Bakr Reham Mohamed Gabr Ola Sayed Ahmed Mostafa Hamed Elberry Ahmed Mahmoud Mayla Mohamed Abouelhoda Abeer A Bahnassy 《World Journal of Gastroenterology》 SCIE CAS 2016年第16期4168-4182,共15页
AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with &#x003b1;-fetoprotein (AFP).METHODS: Serum levels of interleukin (I... AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with &#x003b1;-fetoprotein (AFP).METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and &#x003b2;-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups.RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 &#x000d7; Prot + 0.00108 &#x000d7; sICAM + 0.2574 &#x000d7; &#x003b2;-catenin + 0.01597 &#x000d7; AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 &#x000d7; proteasome + 0.002024 &#x000d7; IL + 0.004096 &#x000d7; sICAM-1 + (4.251 &#x000d7; 10<sup>-4</sup>) &#x000d7; sTNF + 0.02567 &#x000d7; &#x003b2;-catenin + 0.02442 &#x000d7; AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status.CONCLUSION: Our proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection. 展开更多
关键词 Mathematical model Hepatocellular carcinoma ;1 -FETOPROTEIN Soluble intercellular adhesion molecule-1 β -CATENIN INTERLEUKIN-8 Soluble tumor necrosis factor receptor II PROTEASOME
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