AIM:Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are central to the spontaneous resolution of liver fibrosis. The mechanisms involved have been investigated in hepatic...AIM:Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are central to the spontaneous resolution of liver fibrosis. The mechanisms involved have been investigated in hepatic stellate cells (HSC), but not in hepatocytes. We investigated the effects of fibril- and fixed-collagen on MMP-1 and TIMP-1 production in hepatocytes, using the HLE cell line. METHODS: Fibril type I and IV collagen were prepared by HCI digestion of type I and IV collagen, respectively. For fixed-collagen, culture dishes were coated with fibril type I or IV collagen and fixed by ultraviolet. Type I collagenase activity was measured using fluorescein isothiocyanate-labeled type I collagen. MMP-1 and TIMP-1 in HLE cells were measured by a one-step sandwich enzyme immunoassay. RESULTS: Both fibril type I and IV collagen significantly increased type I collagenase activity about two-fold compared with no fibril collagen. The effects of the fibril collagen were not affected by the coating condition. There was no significant difference in the effects on collagenase activity between cells cultured in medium containing fibril type I collagen and those cultured in the presence of type IV collagen. Both types of fibril collagen significantly increased MMP-1 production, and showed more than 10-fold higher levels of MMP-1 than the control. The enhanced MMP-1 production by fibril collagens was unaffected by the coating condition. By contrast, TIMP-1 production was not changed by the addition of fibril type I or IV collagen, and neither was it affected by the coating conditions. Coating with type I collagen significantly suppressed MMP-1 production by almost one-tenth compared with no coating. By contrast, TIMP-1 production was not affected by either the absence of a collagen coat or by increasing the concentration of the coating collagen. CONCLUSION: These results indicated that, in HLE cells, fibril- and fixed-collagen have opposite effects on MMP-1 production without affecting TIMP production. Fibril collagen induced collagenase activity by up-regulation of MMP-1 production without affecting TIMP-1 production. By contrast, fixed collagen reduced MMP-1 production. Our results suggest that hepatocytes might also play an important role in the regulation of the hepatic fibrosis alongside HSC.展开更多
目的:探讨心房颤动患者心房Ⅰ型胶原重构与左心房扩大在房颤发病机制中可能的作用以及它们之间的关系。方法:取24例心脏病患者的右心耳组织(房颤12例,为房颤组;窦性心律12例,为窦律组)。(1)HE染色,观察房颤组与窦律组心肌纤维以及细胞...目的:探讨心房颤动患者心房Ⅰ型胶原重构与左心房扩大在房颤发病机制中可能的作用以及它们之间的关系。方法:取24例心脏病患者的右心耳组织(房颤12例,为房颤组;窦性心律12例,为窦律组)。(1)HE染色,观察房颤组与窦律组心肌纤维以及细胞核、细胞外基质的差异。(2)免疫组化染色,在普通显微镜下观察窦律组与房颤组心房Ⅰ型胶原并使用图像分析系统分析2组的胶原含量分数(collagen volume fraction,CVF),统计2组间Ⅰ型胶原含量分数(CVF-Ⅰ)的差异。(3)对CVF-I与左房直径进行Pearson相关分析。结果:(1)房颤组CVF-Ⅰ高于窦律组(CVF-I:9.29±0.85 vs 6.90±1.47,P<0.01);(2)房颤组心房大于窦律组(6.16±1.01 vs 4.47±0.99,P<0.01);(3)心房大小与Ⅰ型胶原含量不存在相关性(r=0.33,P>0.05)。结论:房颤患者的心房纤维化程度增加、左心房扩大,纤维化与左房扩大可能通过一定的途径,直接或间接参与了房颤的发病过程。展开更多
文摘AIM:Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are central to the spontaneous resolution of liver fibrosis. The mechanisms involved have been investigated in hepatic stellate cells (HSC), but not in hepatocytes. We investigated the effects of fibril- and fixed-collagen on MMP-1 and TIMP-1 production in hepatocytes, using the HLE cell line. METHODS: Fibril type I and IV collagen were prepared by HCI digestion of type I and IV collagen, respectively. For fixed-collagen, culture dishes were coated with fibril type I or IV collagen and fixed by ultraviolet. Type I collagenase activity was measured using fluorescein isothiocyanate-labeled type I collagen. MMP-1 and TIMP-1 in HLE cells were measured by a one-step sandwich enzyme immunoassay. RESULTS: Both fibril type I and IV collagen significantly increased type I collagenase activity about two-fold compared with no fibril collagen. The effects of the fibril collagen were not affected by the coating condition. There was no significant difference in the effects on collagenase activity between cells cultured in medium containing fibril type I collagen and those cultured in the presence of type IV collagen. Both types of fibril collagen significantly increased MMP-1 production, and showed more than 10-fold higher levels of MMP-1 than the control. The enhanced MMP-1 production by fibril collagens was unaffected by the coating condition. By contrast, TIMP-1 production was not changed by the addition of fibril type I or IV collagen, and neither was it affected by the coating conditions. Coating with type I collagen significantly suppressed MMP-1 production by almost one-tenth compared with no coating. By contrast, TIMP-1 production was not affected by either the absence of a collagen coat or by increasing the concentration of the coating collagen. CONCLUSION: These results indicated that, in HLE cells, fibril- and fixed-collagen have opposite effects on MMP-1 production without affecting TIMP production. Fibril collagen induced collagenase activity by up-regulation of MMP-1 production without affecting TIMP-1 production. By contrast, fixed collagen reduced MMP-1 production. Our results suggest that hepatocytes might also play an important role in the regulation of the hepatic fibrosis alongside HSC.
文摘目的:探讨心房颤动患者心房Ⅰ型胶原重构与左心房扩大在房颤发病机制中可能的作用以及它们之间的关系。方法:取24例心脏病患者的右心耳组织(房颤12例,为房颤组;窦性心律12例,为窦律组)。(1)HE染色,观察房颤组与窦律组心肌纤维以及细胞核、细胞外基质的差异。(2)免疫组化染色,在普通显微镜下观察窦律组与房颤组心房Ⅰ型胶原并使用图像分析系统分析2组的胶原含量分数(collagen volume fraction,CVF),统计2组间Ⅰ型胶原含量分数(CVF-Ⅰ)的差异。(3)对CVF-I与左房直径进行Pearson相关分析。结果:(1)房颤组CVF-Ⅰ高于窦律组(CVF-I:9.29±0.85 vs 6.90±1.47,P<0.01);(2)房颤组心房大于窦律组(6.16±1.01 vs 4.47±0.99,P<0.01);(3)心房大小与Ⅰ型胶原含量不存在相关性(r=0.33,P>0.05)。结论:房颤患者的心房纤维化程度增加、左心房扩大,纤维化与左房扩大可能通过一定的途径,直接或间接参与了房颤的发病过程。
