Soon-Pyo Lee

Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells.

Bone morphogenetic proteins (BMPs) that belong to the transforming growth factor-β (TGF-β) superfamily cytokines, play crucial roles in hematopoiesis. However, roles of Smad6 in hematopoiesis remained unknown in contrast to the other inhibitory Smad (I-Smad), Smad7. Here we show that Smad6 inhibits erythropoiesis in human CD34(+) cord blood hematopoietic stem cells (HSCs). Smad6 was specifically expressed in CD34(+) cord blood HSCs, which was correlated with the expression of BMP2/4/6/7 and BMP type I receptor (BMPRI). BMP-specific receptor-regulated Smads (R-Smads), Smad1 and Smad5 in cooperation with Smad4 induced transcription of the Smad6 gene. Instead of affecting cell cycle, apoptosis, self-renewal, and stemness of CD34(+) cells, Smad6 knockdown enhanced, whereas Smad6 overexpression suppressed erythropoiesis in stem cell culture and colony formation assay. Consistently, Smad6 suppressed the expression of the genes essential for erythropoiesis, such as Kruppel-like factor 1 (erythroid) (KLF1/EKLF) and GATA binding protein 2 (GATA-2). Promoter analyses showed that Smad6 repressed Smad5/4-induced transcription of the Klf1 gene. Thus, our data suggest that Smad6 indirectly maintains stemness by preventing spontaneous erythropoiesis in HSCs.

Telomerase and Apoptosis in the Placental Trophoblasts of Growth Discordant Twins

In an effort to investigate the molecular basis of growth discordance in embryos that experience the same uterine environment, we compared telomerase activity and apoptosis in placental trophoblasts obtained from growth discordant twins. Between January 2003 and February 2005, placental tissue from twenty pairs of twins was obtained within thirty minutes of delivery. Eleven cases were classified as growth discordant, with birth weight discordance greater than 20%. Nine cases comprised the control group, with less than 20% discordance. Telomerase and apoptotic activities in placental trophoblasts were analyzed by ELISA and immunoblot. Statistical significance was analyzed by a paired t-test, chisquared test, and ANOVA (SPSS ver 11.0). The average growth discordance was 26.8% in the growth discordant group and 14.4% in the control group. There were no significant differences in maternal age, week of gestation at delivery, parity, or chorionisity between the two groups. In the growth discordant group, the larger twin showed significantly higher telomerase activity (p < 0.01), whereas no significant difference was observed in the control group (p = 0.36). In addition, there was no definitive correlation between telomerase activity and the degree of growth discordance in the larger or smaller twins (R = -0.521 and -0.399, p = 0.15 and 0.25, respectively). The apoptosis proteins Bax and Bcl 2 were detected in both the larger and smaller twins in the growth discordant and control groups. There was no statistically significant difference in Bax expression between the larger and smaller twins (p = 0.25 and 0.92, respectively) for either the growth discordant or the control groups. Bcl 2 expression also showed no significant difference between groups. In conclusion, a tendency toward reduced telomerase activity and increased apoptosis was discovered in placental trophoblasts of the smaller growth-discordant twin, possibility resulting in delayed fetal growth.

Effect of human papillomavirus genotype on severity and prognosis of cervical intraepithelial neoplasia

Objective This study evaluated the effect of the specific human papillomavirus (HPV) genotypes on severity and prognosis in cervical intraepithelial neoplasia (CIN) patients. Methods The medical records of 446 patients treated with loop electrosurgical excision procedure (LEEP) were reviewed. The severity of CIN was categorized as CIN1/CIN2 versus CIN3+ including CIN3 and carcinoma in situ (CIS). HPV genotypes were categorized as 1) low risk, 2) intermediate risk, 3) high risk/HPV 16, 4) high risk/HPV 18, and 5) unclassified. Progression was defined as abnormal cytology, including atypical squamous cells, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. The margin status and progression free survival (PFS) by HPV genotypes were analyzed in 355 women with three months or more of post-treatment records. Results CIN3+ was the most common CIN type (67.7%), and high risk/HPV 16 (26.9%) was the most common genotype. Intermediate risk (P < 0.01), high risk/HPV 16 (P < 0.01) and high risk/HPV 18 (P < 0.01) were significantly more common in women with CIN3+ than CIN1/CIN2. Patients with high risk/HPV 18 showed the highest rate of positive margins (P < 0.01). The margin status proved to be the only statistically significant factor affecting PFS. Conclusion The proportion of positive margins was significantly different by HPV genotypes and highest in high risk/HPV 18 group. CIN patients with high risk/HPV 18 need to be more carefully tracked than patients with the other HPV genotypes.