Objective To study the role of insulin-like growth factor II receptor in free silica-induced transdifferentiation of primary rat lung fibroblasts Methods Rat lung fibroblasts and rat alveolar macrophages were cultured...Objective To study the role of insulin-like growth factor II receptor in free silica-induced transdifferentiation of primary rat lung fibroblasts Methods Rat lung fibroblasts and rat alveolar macrophages were cultured. A transdifferentiation model of primary rat lung fibroblasts was induced by free silica. Levels of a-SMA protein, IGF-liR protein and mRNA were measured by immunocytochemistry, Western blot and RT-PCR, respectively. Lung fibroblasts were treated with Wortmannin. Results The expression levels of a-SMA concentration and decreased after Wortmann and IGF-IIR increased with the increasing free silica n was used. Conclusion The IGF-IIR plays an important role in free silica-induced transdifferentiation of primary rat lung fibroblasts.展开更多
Sixty cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry method using antibodies against IGF-II and HBxAg on formalin-fixed, paraffin-embedded tissue se...Sixty cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry method using antibodies against IGF-II and HBxAg on formalin-fixed, paraffin-embedded tissue sections. 32 HCC and 37 LC were found to be positive to HBxAg, in which the positive rates of IGF-II were 100% (32/32) and 94.6% (35/37) respectively. 28 HCC and 10 LC were found to be HBxAg negative, IGF-II was positive in 23 HCC (83.1%) and 6 LC (60%). The positive expression rates of IGF-II in HBxAg positive tissues were significantly higher than those in HBxAg negative tissues (P<0.05). There were three types of distribution of IGF-II expression in HCC and LC: (1) perinucleus; (2) diffuse in cytoplasm; (3) inside nucleus. IGF-II was highly expressed in most of hyperplastic and neoplastic nodules hepatocytes and some of regeneration nodules. Small polygonal liver cells (SPLCs) were found in the liver tissues surrounding the tumor and cirrhosis and they were positive to both IGF-II and HBxAg. The positive rates of IGF-II in SPLC were 86.4% (38/44) in the HBxAg-positive tissues and 40.5%, (15/37) in the HBxAg-negative tissues. The above findings suggest that IGF-II plays an important role in abnormal proliferation of HCC and SPLC. The relation between IGF-II andHBxAg and the nature of SPLCs are also discussed.展开更多
Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its mo...Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. Methods: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration(nmol/mg protein). Status of human IGF-II promoter 3(P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction(MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. Results: The levels of hepatic IGF-II expression were significantly elevated in the HCC group( P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none(0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA(all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level( r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II( r s =-0.89, P < 0.001) or liver IGF-II level( r s =-0.84, P < 0.001). Conclusions: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.展开更多
基金supported by the Research Fund from theNational Natural Science Foundation of China(#81102109)
文摘Objective To study the role of insulin-like growth factor II receptor in free silica-induced transdifferentiation of primary rat lung fibroblasts Methods Rat lung fibroblasts and rat alveolar macrophages were cultured. A transdifferentiation model of primary rat lung fibroblasts was induced by free silica. Levels of a-SMA protein, IGF-liR protein and mRNA were measured by immunocytochemistry, Western blot and RT-PCR, respectively. Lung fibroblasts were treated with Wortmannin. Results The expression levels of a-SMA concentration and decreased after Wortmann and IGF-IIR increased with the increasing free silica n was used. Conclusion The IGF-IIR plays an important role in free silica-induced transdifferentiation of primary rat lung fibroblasts.
基金This work was supported by National Science Foundation of China(No.3880376)by the Medical Science Foundation fPLA.
文摘Sixty cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry method using antibodies against IGF-II and HBxAg on formalin-fixed, paraffin-embedded tissue sections. 32 HCC and 37 LC were found to be positive to HBxAg, in which the positive rates of IGF-II were 100% (32/32) and 94.6% (35/37) respectively. 28 HCC and 10 LC were found to be HBxAg negative, IGF-II was positive in 23 HCC (83.1%) and 6 LC (60%). The positive expression rates of IGF-II in HBxAg positive tissues were significantly higher than those in HBxAg negative tissues (P<0.05). There were three types of distribution of IGF-II expression in HCC and LC: (1) perinucleus; (2) diffuse in cytoplasm; (3) inside nucleus. IGF-II was highly expressed in most of hyperplastic and neoplastic nodules hepatocytes and some of regeneration nodules. Small polygonal liver cells (SPLCs) were found in the liver tissues surrounding the tumor and cirrhosis and they were positive to both IGF-II and HBxAg. The positive rates of IGF-II in SPLC were 86.4% (38/44) in the HBxAg-positive tissues and 40.5%, (15/37) in the HBxAg-negative tissues. The above findings suggest that IGF-II plays an important role in abnormal proliferation of HCC and SPLC. The relation between IGF-II andHBxAg and the nature of SPLCs are also discussed.
基金supported partly by grants from the National Natural Science Foundation(81673241,81702419,81872738,81873915)the Jiangsu Medical Science(BE2016698)&Graduate Innovation(KYCX17_1934)the International S.&T.Coopera-tion Program(2013DFA32150)of China
文摘Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. Methods: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration(nmol/mg protein). Status of human IGF-II promoter 3(P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction(MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. Results: The levels of hepatic IGF-II expression were significantly elevated in the HCC group( P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none(0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA(all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level( r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II( r s =-0.89, P < 0.001) or liver IGF-II level( r s =-0.84, P < 0.001). Conclusions: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.
