ABSTRACT
As an effective anticancer drug, the clinical limitation of doxorubicin (Dox) is the time- and dose-dependent cardiotoxicity. Yes-associated protein 1 (YAP1) interacts with transcription factor TEA domain 1 (TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced
ABSTRACT
Objective: To investigate the effect of IL-22 on the expression of Amphiregulin (AREG) in HaCaT and further understand its role in psoriasis vulgaris (PsV). Methods: The mRNA expressions of IL-22, IL-22R1, IL-22BP and AREG were detected by RT-qPCR in PsV lesions (n=26) and healthy control (HC) skin specimens (n=15). RT-qPCR and Western blot were applied to detect the expression of AREG in HaCaT cells stimulated with IL-22 (20 ng/mL) and its soluble receptor IL-22BP (20 ng/mL) for 24 h. Results: The mRNA expressions of IL-22 (P<0.001), IL-22R1 (P<0.001) and AREG (P<0.01) were significantly increased respectively by 36 times, 24 times and 15 times in PsV compared with those in HC. In addition, there were positive correlations between the mRNA levels of AREG and IL-22 (r=0.49, P<0.05). IL-22 could upregulate the mRNA level of AREG by 22 times and protein expression by 6 times in HaCaT cells (P<0.01). IL-22BP could inhibit the effect of IL-22 (P<0.05). Conclusion: IL-22 may regulate positively amphiregulin expression of keratinocytes involved in psoriasis, and IL-22BP may inhibit this role as a blocker in treating psoriasis.
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Objective To analyze differentially expressed genes between hilar and distal cholangiocarcinoma and to clarify the molecular mechanism of tumorigenesis. Methods Gene-expression profiles of 3 samples of hilar cholangiocarcinoma and 4 samples of distal cholangiocarcinoma were analyzed using oligo microarray containing 21 329 genes. The differentially expressed genes between the two groups were analyzed using the Significance Analysis of Microarrays (SAM) in order to get the specifically differentially expressed genes. The gene expression presence was verified by real-time PCR (RT-PCR). Results A total of 725 genes of cholangiocarcinoma was regulated significantly compared to normal bile duct. Of them, 244 genes were upregulated and 399 genes were downregualted in both groups; on the other hand, 82 gene expressions between hilar and distal cholangiocarcinoma had significant differences (ratio ≥ 2.0 or ≤ 0.5). The SAM analysis showed that 40 genes, including AREG, EPHA2, SPP1, PACE4, and so on, were identified as differentially regulated between the two groups (q=0). Conclusions These data are helpful for a better understanding of the tumorigenesis of cholangiocarcinoma and contribute to the development of diagnostic and therapeutic strategies. The gene expressions between hilar and distal cholangiocarcinoma are significantly different, which suggests that the two tumors have different molecular mechanisms of tumorigenesis.