Woojin Jeong, Hyein Lee, Sukhee Cho, and Jinsoo SeoMol. Cells 2019; 42(11): 739-746 https://doi.org/10.14348/molcells.2019.0200
Abstract : Significant knowledge about the pathophysiology of Alzheimer’s disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and
Heeju Ryu, Jiyeon Kim, Daehong Kim, Jeong-Eun Lee, and Yeonseok ChungMol. Cells 2019; 42(11): 747-754 https://doi.org/10.14348/molcells.2019.0196
Abstract : The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among CD4+ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemia-associated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.
Byung Chull An, Yongku Ryu, Yeo-Sang Yoon, Oksik Choi, Ho Jin Park, Tai Yeub Kim, Song-In Kim, Bong-Kyu Kim, and Myung Jun ChungMol. Cells 2019; 42(11): 755-762 https://doi.org/10.14348/molcells.2019.0064
Abstract : Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a
Qian Xu, Zhihua Liu, Ling Guo, Rui Liu, Rulei Li, Xiang Chu, Jiajia Yang, Jia Luo, Faming Chen, and Manjing DengMol. Cells 2019; 42(11): 763-772 https://doi.org/10.14348/molcells.2019.0023
Abstract : Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible factor-1α (HIF-1α) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of HIF-1α, vascular endothelial growth factor (VEGF), and RUNX2
Jeong-Woo Park and Young-Seuk BaeMol. Cells 2019; 42(11): 773-782 https://doi.org/10.14348/molcells.2019.0018
Abstract : Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, p21Cip1/WAF1 is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of
Jin-Ik Kim, Randal J. Kaufman, Sung Hoon Back, and Ja-Young MoonMol. Cells 2019; 42(11): 783-793 https://doi.org/10.14348/molcells.2019.0104
Abstract : When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of ATF6α by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human ATF6α N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-hATF6α deletion variant was cleaved to liberate active transcription activator encompassing GV-hATF6α fragment which could translocate into the nucleus. The translocated GV-hATF6α fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-hATF6α(333) represents an innovative tool to investigate regulated intramembrane proteolysis of ATF6α. It can substitute active pATF6(N) binding motif-based reporter cell lines.
Meng Liang and Ke HuMol. Cells 2019; 42(11): 794-803 https://doi.org/10.14348/molcells.2019.0121
Abstract : Ultraviolet light (UV)-induced cellular response has been studied by numerous investigators for many years. Long noncoding RNAs (lncRNAs) are emerging as new regulators of diverse cellular process; however, little is known about the role of lncRNAs in the cellular response to UV treatment. Here, we demonstrate that levels of lncRNA-HOTTIP significantly increases after UV stimulation and regulates the UV-mediated cellular response to UV through the coordinate activation of its neighboring gene Hoxa13 in GC-1 cells (spermatogonia germ cell line). UV-induced, G2/M-phase arrest and early apoptosis can be regulated by lncRNA-HOTTIP and Hoxa13. Furthermore, lncRNA-HOTTIP can up-regulate γ-H2AX and p53 expression via Hoxa13 in UV-irradiated GC-1 cells. In addition, p53 has the ability to regulate the expression of both lncRNA-HOTTIP and Hoxa13
Choa Park, Yejin Lee, Soyeon Je, Shengzhi Chang, Nayoung Kim, Euna Jeong, and Sukjoon YoonMol. Cells 2019; 42(11): 804-809 https://doi.org/10.14348/molcells.2019.0099
Abstract : Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene,
Min Kyung Kim, Bongjun Kim, Jun-Oh Kwon, Min-Kyoung Song, Suhan Jung, Zang Hee Lee, and Hong-Hee KimMol. Cells 2019; 42(11): 810-819 https://doi.org/10.14348/molcells.2019.0189
Abstract : For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. In a microarray approach, we found the suppression of tumorigenicity 5 (ST5) gene is upregulated by receptor activator of nuclear factor-κB ligand (RANKL), the OC differentiation factor. Although the roles of ST5 in cancer and β-cells have been reported, the function of ST5 in bone cells has not yet been investigated. Knockdown of ST5 by siRNA reduced OC differentiation from primary precursors. Moreover, ST5 downregulation decreased expression of NFATc1, a key transcription factor for osteoclastogenesis. In contrast, overexpression of ST5 resulted in the opposite phenotype of ST5 knockdown. In immunocytochemistry experiments, the ST5 protein is co-localized with Src in RANKL-committed cells. In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. ST5 reduction caused a decrease in RANKL-evoked calcium oscillation and inhibited translocation of NFATc1 into the nucleus. Taken together, these findings provide the first evidence of ST5 involvement in positive regulation of osteoclastogenesis via Src/Syk/calcium signaling.