• Journal of Periodontal and Implant Science
• /
• v.31 no.1
• /
• pp.135-148
• /
• 2001

Gingival fibroblasts are major cellular component of gingiva. However, the molecular mechanisms of senescence of human gingival fibroblasts are unknown. Human fibroblasts undergo replicative senescence in vitro after a limited number of population doublings. A reduced rate of proliferation is a prominent phenomenon observed in senescent fibroblasts. This phenomenon is controled by cell cycle regulatory proteins. The purpose of present study was to investigate the effect of replicative senescence on cell cycle progression and to find out its molecular mechanisms in human gingival fibroblasts. Replicative senescence of gingival fibroblasts were induced by subsequent cultures that were repeated up to 18 passage. In the present study, I examined change of cell proliferation, cell activity, cell viability and cell cycle progression during the replicative process. Also, I examined expression of cell cycle regulatory proteins which was estimated by western blot analysis. Cell proliferation, cell activity and cell viability of gingival fibroblasts were notably decreased with increase of population doubling level(PDL). S phase was decreased and G1 phase was increased with increase of PDL. Western blot analysis showed that levels of P16, p21 and p53 of senescent gingival fibroblasts(PDL41, PDL58) were higher than young fibroblasts(PDL27) and cdk4 were lower than young fibroblasts(PDL27). In conclusion, these results suggest that proliferative function of human gingival fibroblasts may be decreased by replicative senescence and its molecular mechanisms may be activatied with p16, p21, p53 and pRB, and repressed wtih cdk4.

• Biotechnology and Bioprocess Engineering:BBE
• /
• v.5 no.4
• /
• pp.253-262
• /
• 2000

Aspergillus is considered to be an attractive host for heterologous protein production because of its safety and ability to secrete large amounts of proteins. In order to obtain high productivity, thus far promoters of amylases have been most widely used in A. oryzae. Recent progress in cloning and expression analysis, including EST sequencing, revealed that glycolytic genes represent some of those most strongly expressed in A. oryzae. Therefore, promoters of glycolytic genes could be important alternatives to promoters of amylases because lower amounts of proteases are produced in the presence of glucose. Several A. oryzae transcription factors responsible for the induction and/or maximum expression of many industrially important genes encoding amylases and proteases have been cloned and characterized. In addition to the transcriptional regulatory factors, the gene encoding the largest subunit of RNa polymerase II, constituting the basic transcription machinery, has also been cloned from A. oryzae. This recently acquired understanding of the details of transcriptional regulatory mechanisms and factors will facilitate engineering flexible controls for the expression of proteins important for the fermentation industries.

• IMMUNE NETWORK
• /
• v.16 no.5
• /
• pp.281-285
• /
• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2265-2268
• /
• 2013

Several lines of evidence indicate that cancer is a multistep process. To survey the mechanisms involving gene alteration and miRNAs in adrenocortical cancer, we focused on transcriptional factors as a point of penetration to build a regulatory network. We derived three level networks: differentially expressed; related; and global. A topology network ws then set up for development of adrenocortical cancer. In this network, we found that some pathways with differentially expressed elements (genetic and miRNA) showed some self-adaption relations, such as EGFR. The differentially expressed elements partially uncovered mechanistic changes for adrenocortical cancer which should guide medical researchers to further achieve pertinent research.

• BMB Reports
• /
• v.50 no.11
• /
• pp.554-559
• /
• 2017

MicroRNAs (miRNAs) are ~22nt-long single-stranded RNA molecules that form a RNA-induced silencing complex with Argonaute (AGO) protein to post-transcriptionally downregulate their target messenger RNAs (mRNAs). To understand the regulatory mechanisms of miRNA, discovering the underlying functional rules for how miRNAs recognize and repress their target mRNAs is of utmost importance. To determine functional miRNA targeting rules, previous studies extensively utilized various methods including high-throughput biochemical assays and bioinformatics analyses. However, targeting rules reported in one study often fail to be reproduced in other studies and therefore the general rules for functional miRNA targeting remain elusive. In this review, we evaluate previously-reported miRNA targeting rules and discuss the biological impact of the functional miRNAs on gene-regulatory networks as well as the future direction of miRNA targeting research.

• BMB Reports
• /
• v.51 no.11
• /
• pp.547-548
• /
• 2018

Phloem network integrates cellular energy status into post-embryonic growth, and development by tight regulation of carbon allocation. Phloem development involves complicated coordination of cell fate determination, cell division, and terminal differentiation into sieve elements (SEs), functional conduit. All of these processes must be tightly coordinated, for optimization of systemic connection between source supplies and sink demands throughout plant life cycle, that has substantial impact on crop productivity. Despite its pivotal role, surprisingly, regulatory mechanisms underlying phloem development have just begun to be explored, and we recently identified a novel translational regulatory network involving RNA G-quadruplex and a zinc-finger protein, JULGI, for phloem development. From this perspective, we further discuss the role of RNA G-quadruplex on post-transcriptional control of phloem regulators, as a potential interface integrating spatial information for asymmetric cell division, and phloem development.

• BMB Reports
• /
• v.38 no.2
• /
• pp.121-127
• /
• 2005

Drosophila protects itself from infection by microbial organisms by means of its pivotal defense, the so-called innate immunity system. This is its sole defense as it lacks an adaptive immunity system such as is found in mammals. The strong conservation of innate immunity systems in organisms from Drosophila to mammals, and the ease with which Drosophila can be manipulated genetically, makes this fly a good model system for investigating the mechanisms of virulence of a number of medically important pathogens. Potentially damaging endogenous and/or exogenous challenges sensed by specific receptors initiate signals via the Toll and/or Imd signaling pathways. These in turn activate the transcription factors Dorsal, Dorsal-related immune factor (Dif) and Relish, culminating in transcription of genes involved in the production of antimicrobial peptides, melanization, phagocytosis, and the cytoskeletal rearrangement required for appropriate responses. Clarifying the regulatory interactions between the various pathways involved is very important for understanding the specificity and termination mechanism of the immune response.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5543-5552
• /
• 2013

Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), $Wnt/{\beta}$-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.

• The Korean Journal of Physiology
• /
• v.11 no.2
• /
• pp.17-22
• /
• 1977

By the intravenous infusion of saline solution through the postcaval vein, the effects of increasing the venous return on the heart rate were studied in the water turtle (Amyda japonica). The following results were obtained: 1) Prior to saline infusion, when the initial heart rate was below $50{\sim}55/min$ the heart rate was increased by the infusion. When the initial rate was above this value no changes in heart rate were observed following the infusion. 2) When the heart rate was decreased by vagal stimulation, the infusion elicited a remarkable increase in the heart rate. 3) Increased heart rate caused by tile infusion was not affected by vagotomy or sympathectomy. 4) These results suggest that the increase in heart rate secondary to increased venous return is under the control of a myogenic regulatory mechanism, not a neural mechanism.

• BMB Reports
• /
• v.56 no.6
• /
• pp.321-325
• /
• 2023

RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face constant cellular decision for the precise control of cellular function and activity. Most eukaryotic cells employ conserved machineries for RNA decay including RNA silencing and RNA quality control (RQC). In plants, RQC monitors endogenous RNAs and degrades aberrant and dysfunctional species, whereas RNA silencing promotes RNA degradation to repress the expression of selected endogenous RNAs or exogenous RNA derived from transgenes and virus. Interestingly, emerging evidences have indicated that RQC and RNA silencing interact with each by sharing target RNAs and regulatory components. Such interaction should be tightly organized for proper cellular survival. However, it is still elusive that how each machinery specifically recognizes target RNAs. In this review, we summarize recent advances on RNA silencing and RQC pathway and discuss potential mechanisms underlying the interaction between the two machineries.