Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely ...Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely involves multiple mechanisms with limited therapies available, and is associated with defects in connective tissue including elastic fibers. This study was designed to investigate the expression of fibulin-5 and lysyl oxidase-like 1 （LOXL1） in the cardinal ligament in samples taken from the POP group compared to the non-POP group. Specimens were obtained during abdominal hysterectomy from the cardinal ligament of 53 women with POP and 25 age- and par- ity- matched women with non-POP among post-menopausal women with benign gynecologic pathology. Protein expression was evaluated using the immunohistochemical staining method. For statistical analyses, chi-square test and Spearman＇s correlation were used with the statistical package SPSS13.0 system. Our results showed that both fibulin-5 and LOXL1 expressions were decreased in the cardinal ligament in the POP group compared to the non- POP group （P 〈 0.05）. The expression of fibulin-5 and LOXL1 were correlated closely with the stage of POP, ac- companied by stress urinary incontinence and frequency of vaginal delivery （P 〈 0.05）, but had no relationship with post-menopausal state （P 〉 0.05）. The expression of fibulin-5 was positively associated with LOXL1 in POP （P 〈 0.05）. We conclude that changes in fibulin-5 and LOXL1 expression may play a role in the development of POP.展开更多
AIM: To elucidate the role of fibulin-5(FBLN-5) as a suppressor of hepatocellular carcinoma(HCC) cell metastasis via integrin.METHODS: The expression of FBLN-5 was determined by immunohistochemistry in 140 HCC samples...AIM: To elucidate the role of fibulin-5(FBLN-5) as a suppressor of hepatocellular carcinoma(HCC) cell metastasis via integrin.METHODS: The expression of FBLN-5 was determined by immunohistochemistry in 140 HCC samples and matched normal tissues, and was further confirmed by RT-PCR and Western blot analyses in various cell lines. Recombinant FBLN-5 was expressed in Escherichia coli BL21(DE3), purified and used in cell attachment assays. Expression of a specific plasmid or a specific si RNA in HCC cells resulted in the overexpression or knockdown of FBLN-5, respectively. Further, the migration and invasion of HCC cells were investigated using the Boyden chamber and transwell assays. The concentration of secreted matrix metalloproteinase 7(MMP-7) was determined using ELISA. RESULTS: FBLN-5 expression was found to be downregulated in HCC. Its expression was significantly correlated with advanced tumor metastasis; this was indicative of poor 5-year overall survival. Recombinant full-length human FBLN-5 promoted the attachment of HCC cells via integrins: it inhibited HCC cell adhesionand migration to fibronectin in a concentrationdependent manner. It also inhibited HCC cell migration and invasion through an integrin-binding arginineglycine-aspartic acid(RGD) motif by downregulating MMP-7. CONCLUSION: These results suggest that lower FBLN-5 expression is an important indicator of poor survival and that FBLN-5 inhibits HCC motility via an integrin-dependent mechanism. RGD-dependent suppression of MMP-7 by FBLN-5 might contribute to the development of new therapeutic strategies for HCC.展开更多
文摘Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely involves multiple mechanisms with limited therapies available, and is associated with defects in connective tissue including elastic fibers. This study was designed to investigate the expression of fibulin-5 and lysyl oxidase-like 1 （LOXL1） in the cardinal ligament in samples taken from the POP group compared to the non-POP group. Specimens were obtained during abdominal hysterectomy from the cardinal ligament of 53 women with POP and 25 age- and par- ity- matched women with non-POP among post-menopausal women with benign gynecologic pathology. Protein expression was evaluated using the immunohistochemical staining method. For statistical analyses, chi-square test and Spearman＇s correlation were used with the statistical package SPSS13.0 system. Our results showed that both fibulin-5 and LOXL1 expressions were decreased in the cardinal ligament in the POP group compared to the non- POP group （P 〈 0.05）. The expression of fibulin-5 and LOXL1 were correlated closely with the stage of POP, ac- companied by stress urinary incontinence and frequency of vaginal delivery （P 〈 0.05）, but had no relationship with post-menopausal state （P 〉 0.05）. The expression of fibulin-5 was positively associated with LOXL1 in POP （P 〈 0.05）. We conclude that changes in fibulin-5 and LOXL1 expression may play a role in the development of POP.
基金Zhejiang Provincial Natural Science Foundation of China,No.LY13H180001Education Bureau of Zhejiang Province,No.N20130416
文摘AIM: To elucidate the role of fibulin-5(FBLN-5) as a suppressor of hepatocellular carcinoma(HCC) cell metastasis via integrin.METHODS: The expression of FBLN-5 was determined by immunohistochemistry in 140 HCC samples and matched normal tissues, and was further confirmed by RT-PCR and Western blot analyses in various cell lines. Recombinant FBLN-5 was expressed in Escherichia coli BL21(DE3), purified and used in cell attachment assays. Expression of a specific plasmid or a specific si RNA in HCC cells resulted in the overexpression or knockdown of FBLN-5, respectively. Further, the migration and invasion of HCC cells were investigated using the Boyden chamber and transwell assays. The concentration of secreted matrix metalloproteinase 7(MMP-7) was determined using ELISA. RESULTS: FBLN-5 expression was found to be downregulated in HCC. Its expression was significantly correlated with advanced tumor metastasis; this was indicative of poor 5-year overall survival. Recombinant full-length human FBLN-5 promoted the attachment of HCC cells via integrins: it inhibited HCC cell adhesionand migration to fibronectin in a concentrationdependent manner. It also inhibited HCC cell migration and invasion through an integrin-binding arginineglycine-aspartic acid(RGD) motif by downregulating MMP-7. CONCLUSION: These results suggest that lower FBLN-5 expression is an important indicator of poor survival and that FBLN-5 inhibits HCC motility via an integrin-dependent mechanism. RGD-dependent suppression of MMP-7 by FBLN-5 might contribute to the development of new therapeutic strategies for HCC.
