Kyung-Sun Heo, Keigi Fujiwara, and Jun-ichi AbeMol. Cells 2014; 37(6): 435-440 https://doi.org/10.14348/molcells.2014.0078
Abstract : Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both
Alexander J.S. Choi, and Stefan W. RyterMol. Cells 2014; 37(6): 441-448 https://doi.org/10.14348/molcells.2014.0104
Abstract : Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-kBdependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 (P2X7R), which results in K+ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer’s disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.
Onju Ham, Chang Youn Lee, Byeong-Wook Song, Se-Yeon Lee, Ran Kim, Jun-Hee Park, Jiyun Lee, Hyang-Hee Seo, Chae Yoon Lee, Byeong-Wook Song, Yong-An Chung, Lee-So Maeng, Min Young Lee, Jongmin Kim, Byeong-Wook Song, Jihwan Hwang, Dong Kyun Woo, and Woochul Chang*Mol. Cells 2014; 37(6): 449-456 https://doi.org/10.14348/molcells.2014.0023
Abstract : The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23btransfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated1 cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.
Hophil Min, Dohyun Han, Yikwon Kim, Jee Yeon Cho, Jonghwa Jin, and Youngsoo KimMol. Cells 2014; 37(6): 457-466 https://doi.org/10.14348/molcells.2014.0035
Abstract : Proteomic analysis is helpful in identifying cancerassociated proteins that are differentially expressed and fragmented that can be annotated as dysregulated networks and pathways during metastasis. To examine metastatic process in lung cancer, we performed a proteomics study by label-free quantitative analysis and N-terminal analysis in 2 human non-small-cell lung cancer cell lines with disparate metastatic potentials?NCI-H1703 (primary cell, stage I) and NCI-H1755 (metastatic cell, stage IV). We identified 2130 proteins, 1355 of which were common to both cell lines. In the label-free quantitative analysis, we used the NSAF normalization method, resulting in 242 differential expressed proteins. For the N-terminal proteome analysis, 325 N-terminal peptides, including 45 novel fragments, were identified in the 2 cell lines. Based on two proteomic analysis, 11 quantitatively expressed proteins and 8 N-terminal peptides were enriched for the focal adhesion pathway. Most proteins from the quantitative analysis were upregulated in metastatic cancer cells, whereas novel fragment of CRKL was detected only in primary cancer cells. This study increases our understanding of the NSCLC metastasis proteome.
Yeon Kyung Na, Hae Sook Hong, Duk Hee Lee, Won Kee Lee, and Dong Sun KimMol. Cells 2014; 37(6): 467-472 https://doi.org/10.14348/molcells.2014.0073
Abstract : Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic- pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and 30 kg/m2. However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.
Na Young Choi, Yo Seph Park, Jae-Sung Ryu, Hye Jeong Lee, Marcos J. Ara?zo-Bravo, Kisung Ko, Dong Wook Han, Hans R. Sch?ler, and Kinarm KoMol. Cells 2014; 37(6): 473-479 https://doi.org/10.14348/molcells.2014.0080
Abstract : Spermatogonial stem cells (SSCs, also called germline stem cells) are self-renewing unipotent stem cells that produce differentiating germ cells in the testis. SSCs can be isolated from the testis and cultured
Doo Hwan Yeom, Su-Jin Im, Soo-Kyoung Kim, and Joon-Hee LeeMol. Cells 2014; 37(6): 480-486 https://doi.org/10.14348/molcells.2014.0105
Abstract : Growth restriction by antibiotics is a common feature that pathogenic bacteria must overcome for survival. The struggle of bacteria to escape from growth restriction eventually results in development of antibiotic-resistance through the expression of a set of genes. Here we found that some physiologically important transcriptional regulators of
Jin-Hwa Choi, Minh-Phuong Nguyen, Dongjin Lee, Goo-Taeg Oh, and You-Mie LeeMol. Cells 2014; 37(6): 487-496 https://doi.org/10.14348/molcells.2014.0119
Abstract : Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout (AGT+/-) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of AGT+/- EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in AGT+/- EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-1α and -2α were downregulated in AGT+/- early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-1α were suppressed in AGT+/- EPCs. In AGT+/- mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.
Nayeon Lee, Jae Woo Park, Hyung Joon Kim, Ju Hun Yeon, Jihye Kwon, Jung Jae Ko, Seung-Hun Oh, Hyun Sook Kim, Aeri Kim, Baek Soo Han, Sang Chul Lee, Noo Li Jeon, and Jihwan SongMol. Cells 2014; 37(6): 497-502 https://doi.org/10.14348/molcells.2014.0137
Abstract : Microfluidics can provide unique experimental tools to visualize the development of neural structures within a microscale device, which is followed by guidance of neurite growth in the axonal isolation compartment. We utilized microfluidics technology to monitor the differentiation and migration of neural cells derived from human embryonic stem cells (hESCs). We co-cultured hESCs with PA6 stromal cells, and isolated neural rosette-like structures, which subsequently formed neurospheres in suspension culture. Tuj1-positive neural cells, but not nestin-positive neural precursor cells (NPCs), were able to enter the microfluidics grooves (microchannels), suggesting that neural cell-migratory capacity was dependent upon neuronal differentiation stage. We also showed that bundles of axons formed and extended into the microchannels. Taken together, these results demonstrated that microfluidics technology can provide useful tools to study neurite outgrowth and axon guidance of neural cells, which are derived from human embryonic stem cells.