Fibrosis mediated by transforming growth factor-beta (TGF-beta) is a common cause of peritoneal dialysis (PD) failure. In a model of peritoneal fibrosis, we tested the effect of Smad7, an inhibitor of TGF-beta signaling, using an ultrasound-microbubble-mediated delivery system. Rats were given daily PD for 4 weeks and received Smad7 or control plasmid transfer. The ultrasound technique enhanced Smad7 expression in a dose-dependent manner in more than 80% of the peritoneal cells after 3 days. The expression decreased by 14 days, but this was corrected by a second gene transfer. The overexpression of Smad7 substantially inhibited Smad2/3 activation, TGF-beta, plasminogen activator inhibitor-1, extracellular matrix, and myofibroblast mRNA, and protein expression in the peritoneal cells. The decreased peritoneal injury included the rise of mass transfer of glucose, a reduction of the ultrafiltration rate, and fibrotic thickening. Our studies suggest that ultrasound-mediated Smad7 gene delivery may be useful in the prevention or treatment of dialysis-induced peritoneal fibrosis.

Abstract. Recent studies have revealed that alternatively activated macrophages (AAMs) are involved in tumor progression. However, the effect of AAMs on the metastasis of prostate cancer is poorly understood. In the present study, the prostate tissues of 42 patients with prostate adenocarcinoma (PCa) were used in the analysis of tumor associated macrophages (TAMs) and AAMs by immunofluorescence. The patients were followed up for 5 years. The associations of TAMs and AAMs with the clinicopathological features and outcome in these cases were evaluated. Immunofluorescent analysis indicated that the mean number of TAMs (CD68-positive cells) in the prostate tissues of PCa patients with metastasis [45.29±7.25 cells/high-power field (HPF)] was significantly higher compared with that of PCa patients without metastasis (33.57±5.25 cells/HPF; P<0.01). The mean numbers of AAMs (CD68-and CD206-positive cells) in the tissues of PCa patients with and without metastasis were 29.43±5.68 and 9.14±5.29 cells/HPF, respectively. In addition, the percentage of AAMs (number of AAMs/number of TAMs) was 65.11±9.68 and 27.32±7.85% in patients with and without metastasis, respectively. The differences in the number and percentage of AAMs between the two groups were statistically significant (P<0.01). The number and percentage of AAMs was positively correlated with tumor grade and serum prostate-specific antigen (PSA) level. Univariate analysis indicated that the level of PSA, Gleason score, metastatic status, T grade, number of TAMs, number of AAMs and percentage of AAMs were predictors of the overall survival. Furthermore, multivariate analyses revealed that Gleason score, level of PSA and number of TAMs were predictors for overall survival rate. These results indicate that TAMs and AAMs may be important in the metastasis of PCa, and that TAMs and AAMs may be used as potential biomarkers of poor prognosis in late-stage PCa patients.

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The transcription factor PU.1, an important member of the ETS family, plays a significant role in the differentiation of immune cells, which include macrophages, neutrophils, dendritic cells, T lymphoid cells, B lymphoid cells and so on. Immune cells are involved in the occurrence and development of diseases, including inflammatory diseases, neoplastic diseases and immune diseases. Therefore, it is particularly crucial to elucidate the roles and mechanisms of PU.1 in immune cells. The elucidation of these mechanisms may lead to the development of more effective therapeutic strategies for the treatment of inflammatory diseases and immune-mediated diseases mediated by various immune cells. With the development of molecular biology, the mechanisms of PU.1 in immune cell differentiation have been further explained. Different levels of PU.1 expression determine the type of immune cell differentiation. PU.1 expression is increased during granulocyte and macrophage differentiation, while it is decreased during T lymphocyte and B lymphocyte differentiation. The present study reviews and discusses the effects of the transcription factor PU.1 on immune cell differentiation.