目的:检测肌腱糖蛋-X(Tenascin-X,TNX)与血管内皮细胞标志物CD34在ApoE基因敲除小鼠(apolipoprotein E gene knock out mice,ApoE^(-/-)mice)动脉粥样硬化斑块形成过程中的动态表达及探讨两者的相关性。方法:高脂饲养ApoE-/-小鼠建立动...目的:检测肌腱糖蛋-X(Tenascin-X,TNX)与血管内皮细胞标志物CD34在ApoE基因敲除小鼠(apolipoprotein E gene knock out mice,ApoE^(-/-)mice)动脉粥样硬化斑块形成过程中的动态表达及探讨两者的相关性。方法:高脂饲养ApoE-/-小鼠建立动脉粥样硬化动物模型为实验组,普通饲料喂养的C57BL/6小鼠为对照组。分别于喂养第8、12、20、28、36周时测量血脂水平,采集主动脉血管标本,油红O染色和HE染色观察主动脉的病理学改变并进行计量组织学及免疫组化分析。结果:实验组低密度脂蛋白(low-density lipoprotein,LDL)、总胆固醇(total cholesterol,TC)水平在各期中均高于对照组(P <0.05)。随着造模时间的延长,实验组斑块面积及斑块面积/管腔面积比值不断增加(斑块面积:F=31.473,P <0.001;斑块面积/管腔面积:F=178.422,P <0.001)。斑块内TNX与CD34的表达量随着饲养时间的增加而增多,两者均在36周时表达最多,并且TNX与CD34阳性微血管均在纤维帽及脂质核心周围高表达且呈正相关(r=0.87,P <0.001)。而对照组中未见明显斑块形成。结论:Tenascin-X和CD34的表达量随着斑块进展而增多,且两者在斑块中的表达区域相似。TNX可能与斑块稳定性密切相关。展开更多
BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipati...BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation,leading to an abnormal distribution and dysfunction of ICC in the diseased colon,which promotes the occurrence and development of STC.展开更多
Background Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating my...Background Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-lβ1 and peroxisome proliferator-activated receptor γ（TGFβ1-PPARγ） pathway in alcoholic cardiomyopathy （ACM）.Methods Experimental animals were divided into control （group A） and tenascin-x knock-out groups （group B）receiving alcohol. Six months post treatment, cardiac ejections fraction （EF）, fractional shortening （FS）, left ventricle end-diastole internal diameter （LVEDd） and collagen column fraction （CVF） were observed. Tenascin-x, smad-3, TGFβ1,smad-7 and PPARγ protein expression levels were detected by Western blotting.Results Six months post treatment, EF and FS values were higher in group B than in group A （P 〈0.05 and P 〈0.01,respectively）, while LVEDd and CVF were lower in group B （P 〈0.05 and P 〈0.01, respectively）. Tenascin-x, smad-3 and TGFβ1 protein expression levels were higher in group A, while smad-7 and PPARY levels were lower than in group B （P〈0.01）, as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ1 （P 〈0.001）.Conclusion Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ1 and downregulation of PPARγ.展开更多
We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing...We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classifed as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome （EDS）. At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X defciency, but the variant identifed in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A 〉 T nucleotide transition in the TNXB gene may be classifed as disease-causing for EDS due to tenascin-X defciency.展开更多
Background: Extracellular matrix (ECM) participates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involvi...Background: Extracellular matrix (ECM) participates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involving a cohort of proteins. ECM proteins are involved in the regulation of neoangiogenesis in physiological and pathological conditions through their interaction with some angiogenic factors. Our aim was to investigate the role of some angiogenesis-related ECM proteins in the remodeling heart. Methods: We examined cardiac tissue samples from 21 explanted human hearts and 10 non-failing hearts before transplantation. Each specimen was submitted to morphological and biomolecular analysis. Results: We demonstrated a reduced expression of α2-chain laminin mRNA in pathological samples that could play an important role in the progression of cardiac failure by contributing to sarcolemma modifications. Reduced expression of tenascin cytotactin (TN-C) and TN-X in explanted hearts indicated chronic cardiac damage and an impaired capacity to stimulate new vessel development. The observed type IV collagen increase was not related to neoangiogenesis, as reflected by the decreased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2. The inverse correlation between heart dimension and VEGF-A immunopositivity seems particularly interesting. Conclusions: Our findings suggest that ECM reacts strongly to ischemic damage in failing hearts through some important modifications of its protein composition. Nevertheless, this reaction cannot completely restore myocardium structure if it is not supported by adequate neoangiogenesis. The decrease in some ECM proteins related to vessel development has a negative effect on postischemic neoangiogenesis and clinical outcome.展开更多
文摘BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation,leading to an abnormal distribution and dysfunction of ICC in the diseased colon,which promotes the occurrence and development of STC.
文摘Background Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-lβ1 and peroxisome proliferator-activated receptor γ（TGFβ1-PPARγ） pathway in alcoholic cardiomyopathy （ACM）.Methods Experimental animals were divided into control （group A） and tenascin-x knock-out groups （group B）receiving alcohol. Six months post treatment, cardiac ejections fraction （EF）, fractional shortening （FS）, left ventricle end-diastole internal diameter （LVEDd） and collagen column fraction （CVF） were observed. Tenascin-x, smad-3, TGFβ1,smad-7 and PPARγ protein expression levels were detected by Western blotting.Results Six months post treatment, EF and FS values were higher in group B than in group A （P 〈0.05 and P 〈0.01,respectively）, while LVEDd and CVF were lower in group B （P 〈0.05 and P 〈0.01, respectively）. Tenascin-x, smad-3 and TGFβ1 protein expression levels were higher in group A, while smad-7 and PPARY levels were lower than in group B （P〈0.01）, as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ1 （P 〈0.001）.Conclusion Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ1 and downregulation of PPARγ.
基金Supported by The National Institute of Child Health and Human Development(NICHD),No.HD02528
文摘We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classifed as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome （EDS）. At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X defciency, but the variant identifed in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A 〉 T nucleotide transition in the TNXB gene may be classifed as disease-causing for EDS due to tenascin-X defciency.
文摘Background: Extracellular matrix (ECM) participates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involving a cohort of proteins. ECM proteins are involved in the regulation of neoangiogenesis in physiological and pathological conditions through their interaction with some angiogenic factors. Our aim was to investigate the role of some angiogenesis-related ECM proteins in the remodeling heart. Methods: We examined cardiac tissue samples from 21 explanted human hearts and 10 non-failing hearts before transplantation. Each specimen was submitted to morphological and biomolecular analysis. Results: We demonstrated a reduced expression of α2-chain laminin mRNA in pathological samples that could play an important role in the progression of cardiac failure by contributing to sarcolemma modifications. Reduced expression of tenascin cytotactin (TN-C) and TN-X in explanted hearts indicated chronic cardiac damage and an impaired capacity to stimulate new vessel development. The observed type IV collagen increase was not related to neoangiogenesis, as reflected by the decreased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2. The inverse correlation between heart dimension and VEGF-A immunopositivity seems particularly interesting. Conclusions: Our findings suggest that ECM reacts strongly to ischemic damage in failing hearts through some important modifications of its protein composition. Nevertheless, this reaction cannot completely restore myocardium structure if it is not supported by adequate neoangiogenesis. The decrease in some ECM proteins related to vessel development has a negative effect on postischemic neoangiogenesis and clinical outcome.
