Background Erythropoietin （EPO） functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective ef...Background Erythropoietin （EPO） functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective effect of erythropoietin on experimental rats enduring spinal cord injury （SCI） by assessing thrombospondin-1 （TSP-1） level and transforming growth factor-β （TGF-β） in the development of a rat model of SCI. Methods Sixty Sprague-Dawley rats were randomly assigned to three groups： sham operation control group, SCI group and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were sacrificed at 24 hours and 7 days subsequently. The Basso, Beattie, and Bresnahan （BBB） scores were examined for locomotor function. Pathological changes were observed after HE staining. The expressions of thrombospondin-2 （TSP-1） and TGF-β were determined by immunohistochemical staining and Western blotting. Results Slighter locomotor dysfunction was discovered and it was recovered abruptly as higher BBB scores were found in the EPO treatment group than in the SCI group （P 〈0.01）. Pathologically, progressive disruption of the dorsal white matter and regeneration of a few neurons were also observed in SCI rats. TSP-1 and TGF-β expression increased at 24 hours and 7 days after SCI in the injured segment, and it was higher in the SCI group than in the EPO treatment group. Spinal cord samples from the animals demonstrated a TSP-1 optical density of 112.2±6.8 and TSP-1 positive cells of 5.7±1.3 respectively. After injury, the TSP-1 optical density and cell number increased to 287.2±14.3/mm^2 and 23.2±2.6/mm^2 at 24 hours and to 232.1±13.2/mm^2 and 15.2±2.3/mm^2 at 7 days respectively. When EPO treated rats compared with the SCI rats, the TSP-1 optical density and cell number decreased to 213.1 ±11.6/mm^2 and 11.9±1.6/mm^2 at 24 hours and to 189.9±10.5/mm^2 and 9.3±1.5/mm^2 at 7 days, respectively （P 〈0.01）. In the SCI ra展开更多
Objective To investigate the effects of YOD1 overexpression on the proliferation and migration of human oral keratinocytes（HOKs）, and to clarify whether the mechanisms involve transforming growth factor-β（TGF-β）...Objective To investigate the effects of YOD1 overexpression on the proliferation and migration of human oral keratinocytes（HOKs）, and to clarify whether the mechanisms involve transforming growth factor-β（TGF-β） signaling. Methods HOKs were transfected with the plasmid p EGFP-N3-YOD1 containing YOD1. The mR NA levels of YOD1 and TGF-β were determined by q PCR. The protein expressions of YOD1, TGF-β, Smad2/3, Smad4, and phospho-Smad2/3 were determined by western blotting. Cell proliferation and migration were evaluated by Cell Counting Kit-8 assay and wound healing assay, respectively. Results The m RNA and protein levels of YOD1 were higher in HOKs transfected with YOD1. YOD1 overexpression significantly enhanced the migration of HOKs. The mR NA and protein levels of TGF-β3 were increased by YOD1 overexpression. HOKs transfected with YOD1 exhibited increased phospho-Smad2/3 levels. Conclusion YOD1 overexpression enhances cell migration by promoting TGF-β3 signaling which may play an important role in lip and palate formation. YOD1 mutation may contribute to aberrant TGF-β3 signaling associated with decreased cell migration resulting in NSCLP.展开更多
目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个...目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个组,分别为模型组,杜仲多糖高、中、低剂量组及秋水仙碱组每组10只。秋水仙碱组（1.0×10^-4g·kg^-1）,杜仲多糖高、中、低剂量组（0.14,0.07,0.035 g·kg^-1）分别连续灌胃给药8周后收集样本,测定法大鼠体质量及计算肝脏系数;采用酶联免疫吸附测定（ELISA）检测血清白细胞介素-6（IL-6）,高迁移率族蛋白B1（high-mobility group box 1,HMGB1）,脂多糖（LPS）,肝组织基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）水平;逆转录聚合酶链式反应（RT-PCR）技术分析各组大鼠肝组织Ⅰ,Ⅲ型胶原蛋白,MMP-1,TIMP-1及转化生长因子-β1（TGF-β1）mRNA表达情况。结果：与正常组比较,CCl4能显著降低实验大鼠体质量（P〈0.01）,提高肝脏系数（P〈0.01）;杜仲多糖能显著增加HF模型的体质量（P〈0.01）,显著降低HF模型肝脏系数（P〈0.01）;ELISA检测表明,杜仲多糖能显著降低肝纤维化大鼠血清IL-6,HMGB1及LPS含量（P〈0.01）;RT-PCR检测结果显示,杜仲多糖及秋水仙碱能显著降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA含量（P〈0.05）,明显提高MMP-1含量（P〈0.05,P〈0.01）,且呈量效关系。结论：杜仲多糖具有显著的抗肝纤维化作用,其作用机制可能与抑制降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA表达有关。展开更多
α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironme...α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.展开更多
基金This study was supported by grants from the Major Science Research Program of Zhejiang Province （No. 2006C23029）, Medical Science Foundation of Zhejiang Province （No. 2005HN007） and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.
文摘Background Erythropoietin （EPO） functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective effect of erythropoietin on experimental rats enduring spinal cord injury （SCI） by assessing thrombospondin-1 （TSP-1） level and transforming growth factor-β （TGF-β） in the development of a rat model of SCI. Methods Sixty Sprague-Dawley rats were randomly assigned to three groups： sham operation control group, SCI group and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were sacrificed at 24 hours and 7 days subsequently. The Basso, Beattie, and Bresnahan （BBB） scores were examined for locomotor function. Pathological changes were observed after HE staining. The expressions of thrombospondin-2 （TSP-1） and TGF-β were determined by immunohistochemical staining and Western blotting. Results Slighter locomotor dysfunction was discovered and it was recovered abruptly as higher BBB scores were found in the EPO treatment group than in the SCI group （P 〈0.01）. Pathologically, progressive disruption of the dorsal white matter and regeneration of a few neurons were also observed in SCI rats. TSP-1 and TGF-β expression increased at 24 hours and 7 days after SCI in the injured segment, and it was higher in the SCI group than in the EPO treatment group. Spinal cord samples from the animals demonstrated a TSP-1 optical density of 112.2±6.8 and TSP-1 positive cells of 5.7±1.3 respectively. After injury, the TSP-1 optical density and cell number increased to 287.2±14.3/mm^2 and 23.2±2.6/mm^2 at 24 hours and to 232.1±13.2/mm^2 and 15.2±2.3/mm^2 at 7 days respectively. When EPO treated rats compared with the SCI rats, the TSP-1 optical density and cell number decreased to 213.1 ±11.6/mm^2 and 11.9±1.6/mm^2 at 24 hours and to 189.9±10.5/mm^2 and 9.3±1.5/mm^2 at 7 days, respectively （P 〈0.01）. In the SCI ra
基金supported by National Natural Science Foundations of China[No.81273103]the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Objective To investigate the effects of YOD1 overexpression on the proliferation and migration of human oral keratinocytes（HOKs）, and to clarify whether the mechanisms involve transforming growth factor-β（TGF-β） signaling. Methods HOKs were transfected with the plasmid p EGFP-N3-YOD1 containing YOD1. The mR NA levels of YOD1 and TGF-β were determined by q PCR. The protein expressions of YOD1, TGF-β, Smad2/3, Smad4, and phospho-Smad2/3 were determined by western blotting. Cell proliferation and migration were evaluated by Cell Counting Kit-8 assay and wound healing assay, respectively. Results The m RNA and protein levels of YOD1 were higher in HOKs transfected with YOD1. YOD1 overexpression significantly enhanced the migration of HOKs. The mR NA and protein levels of TGF-β3 were increased by YOD1 overexpression. HOKs transfected with YOD1 exhibited increased phospho-Smad2/3 levels. Conclusion YOD1 overexpression enhances cell migration by promoting TGF-β3 signaling which may play an important role in lip and palate formation. YOD1 mutation may contribute to aberrant TGF-β3 signaling associated with decreased cell migration resulting in NSCLP.
文摘目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个组,分别为模型组,杜仲多糖高、中、低剂量组及秋水仙碱组每组10只。秋水仙碱组（1.0×10^-4g·kg^-1）,杜仲多糖高、中、低剂量组（0.14,0.07,0.035 g·kg^-1）分别连续灌胃给药8周后收集样本,测定法大鼠体质量及计算肝脏系数;采用酶联免疫吸附测定（ELISA）检测血清白细胞介素-6（IL-6）,高迁移率族蛋白B1（high-mobility group box 1,HMGB1）,脂多糖（LPS）,肝组织基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）水平;逆转录聚合酶链式反应（RT-PCR）技术分析各组大鼠肝组织Ⅰ,Ⅲ型胶原蛋白,MMP-1,TIMP-1及转化生长因子-β1（TGF-β1）mRNA表达情况。结果：与正常组比较,CCl4能显著降低实验大鼠体质量（P〈0.01）,提高肝脏系数（P〈0.01）;杜仲多糖能显著增加HF模型的体质量（P〈0.01）,显著降低HF模型肝脏系数（P〈0.01）;ELISA检测表明,杜仲多糖能显著降低肝纤维化大鼠血清IL-6,HMGB1及LPS含量（P〈0.01）;RT-PCR检测结果显示,杜仲多糖及秋水仙碱能显著降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA含量（P〈0.05）,明显提高MMP-1含量（P〈0.05,P〈0.01）,且呈量效关系。结论：杜仲多糖具有显著的抗肝纤维化作用,其作用机制可能与抑制降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA表达有关。
基金funded by National Nature Science Foundation of China (Grant Nos 30970705, 11172190, 81371171, and 81371172)
文摘α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.
