IL-6 induced angiotensinogen expression in primary cultures of mouse hepatocytes.

<p>(A) Time course of IL-6-induced (10 ng/ml) angiotensinogen protein expression as detected by enzyme immunoassay (n = 3/group). (B) Dose response of IL-6-induced angiotensinogen protein expression after 24 hours of culture, as detected by enzyme immunoassay. Comparisons are between the indicated groups. *<i>P</i><0.05, n = 3.</p

Effect of IL-6-related signaling inhibition on angiotensinogen protein expression and liver regeneration in remnant livers after 70% partial hepatectomy in mice.

<p>Mice were pretreated with chemical inhibitors of JAK2 (AG490, 10 mg/kg subcutaneously), p38 (intraperitoneal SB203580, 15 mg/kg), and STAT3 (intraperitoneal 5,15-DPP, 15 mg/kg) for 4 hours prior to partial hepatectomy. (A) Serum angiotensinogen levels of mice pretreated with different chemical inhibitors (AG490, SB203580, and 5,15-DPP) as detected by enzyme immunoassay. (B) Changes in the ratio of remnant to original liver weight after 70% partial hepatectomy. Remnant liver weight was estimated retrospectively from the excised liver weight after 70% PH. Data are presented as mean ± S.D., and comparisons were made between groups as indicated. *<i>P</i><0.05. (C) Ki-67 staining of regenerated liver tissue sections of the indicated group. Magnification, 400x. (D) Quantification of Ki-67 staining. Data presented here are the quantification of Ki-67-positive nuclei per high-power field. Data are presented as mean percentage of positive nuclei ± S.D., and comparisons were made between groups as indicated. *<i>P</i><0.05.</p

Signal transduction pathways involved in IL-6-induced angiotensinogen expression in primary cultures of mouse hepatocytes.

<p>(A) Inhibition effects of chemical inhibitors 1 to 6 on IL-6-activated signaling mediators detected by Western blotting and quantified by calculating the ratios of phosphorylated/non-phosphorylated protein forms. The ratio in lane 1 is defined as 1. Comparison is between lanes 2 and 3 in each group. *<i>P</i><0.05, n = 3. (B) The effects of different chemical inhibitors on IL-6-induced angiotensinogen protein expression as detected by enzyme immunoassay. Comparison is between the indicated groups. *<i>P</i><0.05, n = 3.</p

Serum IL-6 and angiotensinogen levels, angiotenisogen mRNA and protein expression in remnant livers after 70% partial hepatectomy in mice.

<p>(A) Serum angiotensinogen levels detected by enzyme immunoassay (n = 5/group). (B) Angiotensinogen mRNA detected by reverse transcription-polymerase chain reaction quantified by calculating the ratios of angiotensinogen/GAPDH. (C) Angiotensinogen protein expression detected by Western blot and quantified by calculating the ratios of angiotensinogen/ß-actin. The ratio in lane 1 is defined as 1. Comparison is between the time 0 group and specified time periods. *<i>P</i><0.05, n = 5.</p

Notch3 overexpression causes arrest of cell cycle progression by inducing Cdh1 expression in human breast cancer cells

<p>Uncontrolled cell proliferation, genomic instability and cancer are closely related to the abnormal activation of the cell cycle. Therefore, blocking the cell cycle of cancer cells has become one of the key goals for treating malignancies. Unfortunately, the factors affecting cell cycle progression remain largely unknown. In this study, we have explored the effects of Notch3 on the cell cycle in breast cancer cell lines by 3 methods: overexpressing the intra-cellular domain of Notch3 (N3ICD), knocking-down Notch3 by RNA interference, and using X-ray radiation exposure. The results revealed that overexpression of Notch3 arrested the cell cycle at the G0/G1 phase, and inhibited the proliferation and colony-formation rate in the breast cancer cell line, MDA-MB-231. Furthermore, overexpressing N3ICD upregulated Cdh1 expression and resulted in p27^Kip accumulation by accelerating Skp2 degradation. Conversely, silencing of Notch3 in the breast cancer cell line, MCF-7, caused a decrease in expression levels of Cdh1 and p27^Kipat both the protein and mRNA levels, while the expression of Skp2 only increased at the protein level. Correspondingly, there was an increase in the percentage of cells in the G0/G1 phase and an elevated proliferative ability and colony-formation rate, which may be caused by alterations of the Cdh1/Skp2/p27 axis. These results were also supported by exposing MDA-MB-231 cells or MCF-7 treated with siN3 to X-irradiation at various doses. Overall, our data showed that overexpression of N3ICD upregulated the expression of Cdh1 and caused p27^Kip accumulation by accelerating Skp2 degradation, which in turn led to cell cycle arrest at the G0/G1 phase, in the context of proliferating breast cancer cell lines. These findings help to illuminate the precision therapy targeted to cell cycle progression, required for cancer treatment.</p