维生素D及维生素D受体(vitamin D receptor,VDR)介导的生物效应参与调节体内多个病理生理过程,包括钙磷代谢、免疫调控、抗炎、抗感染、肿瘤预防等。自噬是真核细胞溶酶体介导的一种分解代谢途径,分为巨自噬、微自噬及分子伴侣介导的自...维生素D及维生素D受体(vitamin D receptor,VDR)介导的生物效应参与调节体内多个病理生理过程,包括钙磷代谢、免疫调控、抗炎、抗感染、肿瘤预防等。自噬是真核细胞溶酶体介导的一种分解代谢途径,分为巨自噬、微自噬及分子伴侣介导的自噬3种类型。自噬有助于维持细胞能量及新陈代谢,炎症、感染、肿瘤等多种病理过程均与自噬功能障碍密切相关。维生素D/VDR通过调节炎症因子影响自噬,调节自噬的不同阶段,在自身免疫性疾病、糖尿病、心血管疾病、肿瘤等炎症相关疾病中发挥重要作用。展开更多
Objective To explore the effect of TGF-a1 on the mRNA and prot ei n expression of connective tissue growth factor (CTGF) in human peritoneal mesot helial cells (HPMCs) and the probable mechanism. Methods Greater oment...Objective To explore the effect of TGF-a1 on the mRNA and prot ei n expression of connective tissue growth factor (CTGF) in human peritoneal mesot helial cells (HPMCs) and the probable mechanism. Methods Greater omenta from hea lthy adults were used for primary culture of HPMCs. The third generation cells w ere stimulated by 5 ng/ml TGF-a1. Immunohistochemistry, Western blot, ELISA an d RT-PCR were employed to examine the follows:the mRNA and protein expression o f CTGF, the mRNA and protein expression of fibronectin (FN) and collagen type Ⅰ (ColⅠ), the protein expression of p-Smad2/3 and its migration in HPMCs. Result s (1)The mRNA expression of CTGF in the treatment groups increased obviously a s compared to the control group, and peaked at 48 h. (2)The protein expression of intracellular CTGF in the control group was very little, whereas it increase d markedly 24 h after TGF-a1 stimulation, and peaked at 48 h. The mRNA express ion of intracellular FN, and the protein expression of supernatent FN, as well a s the mRNA and protein expression of intracellular ColⅠin the treatment group u p-regulated significantly in a time dependent manner as compared to those in th e control group. (3)p-Smad2/3 in HPMCs hardly expressed in the control group( 3%p-Smad2/3-positive cells), and remarkably expressed 15 min after TGF-a1 s timulation(29%), peaked at 1 h (84%) and then decreased after 2 h(37%). Meanw hile, p-Smad2/3 mainly distributed in cytoplasm at 15 min, concentrated in cell nucleus and peri-nucleus at 1 h, and distributed in cytoplasm again at 2 h. Co nclusions TGF-a1 can induce the mRNA and protein expression of CTGF in the pro gression of human peritoneal fibrosis. The probably mechanism is that signaling through Smad pathway in HPMCs can be activated by TGF-a1 stimulation.展开更多
目的探讨两种尿毒症毒素晚期糖基化终产物(advanced glycation end products,AGE)和同型半胱氨酸(homocysteine,Hcy)在致血管内皮细胞损伤的过程中是否具有协同作用。方法不同浓度的AGE修饰牛血清白蛋白(AGE-BSA)和Hcy单独或联合作用于...目的探讨两种尿毒症毒素晚期糖基化终产物(advanced glycation end products,AGE)和同型半胱氨酸(homocysteine,Hcy)在致血管内皮细胞损伤的过程中是否具有协同作用。方法不同浓度的AGE修饰牛血清白蛋白(AGE-BSA)和Hcy单独或联合作用于人脐静脉内皮细胞株ECV304细胞,检测各组上清液NO浓度和脂质过氧化终产物丙二醛(MDA)含量及细胞凋亡百分率。结果AGE+Hcy联合干预组的细胞凋亡率明显高于单独AGE和Hcy干预组(P<0.01),MDA含量也显著高于AGE干预组(P<0.05)和Hcy干预组(P<0.01),联合组干预组NO浓度则明显低于单独干预组(P<0.01)。结论AGE和Hcy均参与了血管内皮细胞的损伤,两者具有协同效应,上述效应可能与氧化应激有关,推测终末期肾病(ESRD)患者AGE和Hcy的升高可能是加速该人群动脉粥样硬化发生发展的重要因素。展开更多
文摘维生素D及维生素D受体(vitamin D receptor,VDR)介导的生物效应参与调节体内多个病理生理过程,包括钙磷代谢、免疫调控、抗炎、抗感染、肿瘤预防等。自噬是真核细胞溶酶体介导的一种分解代谢途径,分为巨自噬、微自噬及分子伴侣介导的自噬3种类型。自噬有助于维持细胞能量及新陈代谢,炎症、感染、肿瘤等多种病理过程均与自噬功能障碍密切相关。维生素D/VDR通过调节炎症因子影响自噬,调节自噬的不同阶段,在自身免疫性疾病、糖尿病、心血管疾病、肿瘤等炎症相关疾病中发挥重要作用。
文摘Objective To explore the effect of TGF-a1 on the mRNA and prot ei n expression of connective tissue growth factor (CTGF) in human peritoneal mesot helial cells (HPMCs) and the probable mechanism. Methods Greater omenta from hea lthy adults were used for primary culture of HPMCs. The third generation cells w ere stimulated by 5 ng/ml TGF-a1. Immunohistochemistry, Western blot, ELISA an d RT-PCR were employed to examine the follows:the mRNA and protein expression o f CTGF, the mRNA and protein expression of fibronectin (FN) and collagen type Ⅰ (ColⅠ), the protein expression of p-Smad2/3 and its migration in HPMCs. Result s (1)The mRNA expression of CTGF in the treatment groups increased obviously a s compared to the control group, and peaked at 48 h. (2)The protein expression of intracellular CTGF in the control group was very little, whereas it increase d markedly 24 h after TGF-a1 stimulation, and peaked at 48 h. The mRNA express ion of intracellular FN, and the protein expression of supernatent FN, as well a s the mRNA and protein expression of intracellular ColⅠin the treatment group u p-regulated significantly in a time dependent manner as compared to those in th e control group. (3)p-Smad2/3 in HPMCs hardly expressed in the control group( 3%p-Smad2/3-positive cells), and remarkably expressed 15 min after TGF-a1 s timulation(29%), peaked at 1 h (84%) and then decreased after 2 h(37%). Meanw hile, p-Smad2/3 mainly distributed in cytoplasm at 15 min, concentrated in cell nucleus and peri-nucleus at 1 h, and distributed in cytoplasm again at 2 h. Co nclusions TGF-a1 can induce the mRNA and protein expression of CTGF in the pro gression of human peritoneal fibrosis. The probably mechanism is that signaling through Smad pathway in HPMCs can be activated by TGF-a1 stimulation.
文摘目的探讨两种尿毒症毒素晚期糖基化终产物(advanced glycation end products,AGE)和同型半胱氨酸(homocysteine,Hcy)在致血管内皮细胞损伤的过程中是否具有协同作用。方法不同浓度的AGE修饰牛血清白蛋白(AGE-BSA)和Hcy单独或联合作用于人脐静脉内皮细胞株ECV304细胞,检测各组上清液NO浓度和脂质过氧化终产物丙二醛(MDA)含量及细胞凋亡百分率。结果AGE+Hcy联合干预组的细胞凋亡率明显高于单独AGE和Hcy干预组(P<0.01),MDA含量也显著高于AGE干预组(P<0.05)和Hcy干预组(P<0.01),联合组干预组NO浓度则明显低于单独干预组(P<0.01)。结论AGE和Hcy均参与了血管内皮细胞的损伤,两者具有协同效应,上述效应可能与氧化应激有关,推测终末期肾病(ESRD)患者AGE和Hcy的升高可能是加速该人群动脉粥样硬化发生发展的重要因素。