Prickle1 stunts limb growth through alteration of cell polarity and gene expression

Background: Wnt/PCP signaling plays a critical role in multiple developmental processes, including limb development. Wnt5a, a ligand of the PCP pathway, signals through the Ror2/Vangl2 or the Vangl2/Ryk complex to regulate limb development along the proximal‐distal axis in mice. Based on the interaction between Van Gogh and Prickle in Drosophila, we hypothesized the vertebrate Prickle1 has a similar function as Vangl2 in limb development. Results: We show Prickle1 is expressed in the skeletal condensates that will differentiate into chondrocytes and later form bones. Disrupted Prickle1 function in Prickle1^C251X/C251X mouse mutants alters expression of genes such as Bmp4, Fgf8, Vangl2, and Wnt5a. These expression changes correlate with shorter and wider bones in the limbs and loss of one phalangeal segment in digits 2–5 of Prickle1C251X mutants. These growth defects along the proximal‐distal axis are also associated with increased cell death in the growing digit tip, reduced cell death in the interdigital membrane, and disrupted chondrocyte polarity. Conclusions: We suggest Prickle1 is part of the Wnt5a/PCP signaling, regulating cell polarity and affecting expression of multiple factors to stunt limb growth through altered patterns of gene expression, including the PCP genes Wnt5a and Vangl2. Developmental Dynamics 242:1293–1306, 2013. © 2013 Wiley Periodicals, Inc.     

Eicosanoids: an emerging role in dendritic cell biology

The arachidonic acid (AA)-derived metabolites, termed eicosanoids, are potent lipid mediators with a key role in immune and inflammatory responses. In the immune system, eicosanoids such as prostaglandins (PGs) and leukotrienes (LTs) are produced predominately by antigen-presenting cells (APC), including macrophages and dendritic cells (DC). DC constitute a family of bone marrow-derived professional APC that play a critical role in the induction and modulation of both innate and adaptive immunity. For many years, macrophages were considered as major producers of eicosanoids that are thought to drastically affect their function. Studies concerning the modulation of DC biology by eicosanoids show that PGs and LTs have the potential to affect the maturation, cytokine-producing capacity, Th cell-polarizing ability, and migration of DC. In addition, the development of DC from bone marrow progenitors appears to be under the control of some eicosanoids. Understanding the actions of eicosanoids and their receptors on APC functions is crucial for the generation of efficient DC for therapeutic purposes in patients. In this review, we summarize the current understanding of how DC functions are modulated by eicosanoids.     

表皮生长因子对肝星状细胞基质分解素－1及其抑制因子基因表达调节的影响

目的：了解表皮生长因子（EGF）对肝星状细胞基质分解素－1（MMP₃）及金属蛋白酶组织抑制因子－1（TIMP₁）基因表达的影响。方法：在培养的肝星状细胞系中加入EGF，于不同的时间点收集细胞，提取总RNA；用逆转录定量PCR方法测定基质分解素－1及TIMP₁的基因表达水平。结果：EGF组肝星状细胞MMP₃基因表达水平在8 h、24 h、48 h、72 h 4个时点均明显高于对照组；24 h达高峰，为对照组的3倍。EGF组肝星状细胞TIMP₁的基因表达水平在上述几个时点亦明显高于对照组；24 h达高峰，为对照组的2倍。结论：EGF在体外可增强肝星状细胞基质分解素－1及TIMP₁基因的表达。     

桃核承气汤对Bcl-2和增殖细胞核抗原蛋白表达的影响

目的探讨桃核承气汤(THCQT)对S180荷瘤小鼠环磷酰胺化疗后的Bcl-2和增殖细胞核抗原(PCNA)蛋白表达的影响.方法建立小鼠S180肿瘤模型,采用免疫组织化学方法测定S180小鼠Bcl-2和PCNA蛋白表达的情况.结果 Bcl-2蛋白的表达THCQT组与模型组比较t=5.29,P＜0.01,差异有统计学意义,T...     

The role of nuclear lamin B1 in cell proliferation and senescence

Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary. These results demonstrate the importance of LB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway.     

Human RCAN3 gene expression and cell growth in endothelial cells

Regulator of calcineurin 3 (RCAN3) belongs to the human RCAN gene family, which also includes RCAN1 and RCAN2. All three members interact with and inhibit calcineurin. Based on this effect, several studies have demonstrated a role for RCAN1 and RCAN2 on inflammation, using human umbilical vein endothelial cells (HUVECs) as a model. RCAN1 and 2 are strongly induced by vascular endothelial growth factor (VEGF), inhibit cell proliferation and down-regulate many pro-inflammatory and pro-angiogenic genes. The present work is the first study to investigate the role of RCAN3 on inflammation in HUVECs. RCAN3 isoforms have been characterized and quantified in HUVECs; only those with the same frame are expressed and show a peculiar expression pattern. RCAN3 inhibits HUVEC proliferation both basally and under VEGF or phorbol 12-myristate 13-acetate-stimulated conditions, however it does not modulate gene expression of the chosen inflammatory genes. Results indicate an interesting role for RCAN3 in modulating HUVEC proliferation, independently from the inflammatory and angiogenic processes.     

5-Aza-CdR抑制HepG2细胞DLK1基因表达及细胞生长

目的 探讨去甲基化药物5-氮杂-2’-脱氧胞苷(5-Aza-CdR)对DLK1基因及肝癌细胞系HepG2增殖、侵袭的影响.方法 不同浓度的5-Aza-CdR及PBS作用HepG2细胞后,RT-PCR、Western blot检测DLK1基因及蛋白的表达水平;MTT、Transwell和流式细胞术检测HepG2细胞的生长、侵袭力及细胞周期的变化.结果 HepG2细胞经5-Aza-CdR处理后,DLK1 mRNA、蛋白表达量降低;MTT试验显示细胞生长速度依5-Aza-CdR浓度出现不同程度减慢;流式结果表明G1期细胞减少,S期细胞增加,出现S期阻滞;Transwell证实侵袭能力显著降低(P＜0.05).结论 去甲基化药物5-Aza-CdR能有效地抑制DLK1基因的表达,从而抑制肿瘤细胞HepG2生长、增殖、侵袭能力.     

TFPI-2基因的表达调控及其在疾病中的作用

组织因子途径抑制物-2（TFPI-2）是一种Kunitz型丝氨酸蛋白酶抑制剂,在动脉粥样硬化、肿瘤浸润转移和血管新生等病理生理过程中发挥重要作用。细胞外信号可通过调节启动子或信号传导通路等多种因素调节TFPI-2基因的表达,其调控机制成为近几年的研究热点之一。     

The role of AP-1 in matrix metalloproteinase gene expression

In an effort to understand the mechanism of matrix metalloproteinase (MMP) induction, lapine synoviocytes were isolated and incubated with phorbol myristate acetate (PMA) and autocrine cell-activating factors (CAF), agents which significantly increase MMP mRNA abundance. AP-1 complexes, formed by c-fos and c-jun which bind to 5 residues of the MMP genes, seem causally related to MMP gene expression in response to PMA. However, although AP-1 DNA binding activity is strongly induced following exposure of synoviocytes to CAF, MMP gene expression in response to CAF does not correlate well with AP-1 activity and is not inhibited by antisense DNA to fos and jun. We hypothesize that there is a CAF-response factor involved in MMP gene expression and that this factor competes with the binding of the AP-1 complex to its target response element.     

An emerging role of PARK2 in cancer

PARK2 (PARKIN) is an E3 ubiquitin ligase involved in multiple signaling pathways and cellular processes. Activity of PARK2 is tightly regulated through inter- and intra-molecular interactions. Dysfunction of PARK2 is associated with the progression of parkinsonism. Notably, frequent PARK2 inactivation has been identified in various human cancers. Park2-deficient mice are more susceptible to tumorigenesis, indicating its crucial role as a tumor suppressor. However, biological studies also show that PARK2 possesses both pro-survival and growth suppressive functions. Here, we summarize the genetic lesions of PARK2 in human cancers and discuss the current knowledge of PARK2 in cancer progression. We further highlight future efforts for the study of PARK2 in cancer.     

The emerging role of microRNAs in immune cell development and differentiation

MicroRNAs (miRNAs) are small RNA strands (20–25 nucleotides) that regulate gene expression by translational repression as well as by messenger RNA degradation. This review will examine the application and function of miRNAs in immune cell development and differentiation.