• 제목/요약/키워드: Focal adhesion

검색결과 92건 처리시간 0.024초

인간치은섬유아세포의 다양한 세포행동 관련 유전자발현에 마이크로그루브-파이브로넥틴 복합 티타늄표면이 미치는 영향에 대한 연구 (A study on the effect of microgroove-fibronectin complex titanium plate on the expression of various cell behavior-related genes in human gingival fibroblasts)

  • 황유정;이원중;이성복;이석원
    • 구강회복응용과학지
    • /
    • 제38권3호
    • /
    • pp.150-161
    • /
    • 2022
  • 목적:인간 치은섬유아세포의 세포활동에 관련된 다양한 유전자들의 발현에 마이크로그루브-파이브로넥틴 복합 표면이 미치는 영향을 확인하고자 하였다. 연구 재료 및 방법: 평활한 티타늄시편(NE0), 산처리만 시행한 티타늄시편(E0), 마이크로그루브 및 산처리된 티타늄시편(E60/10), 파이브로넥틴을 고정시킨 평활한 티타늄시편(NE0FN), 산처리 및 파이브로넥틴을 고정시킨 티타늄시편(E0FN), 그리고 마이크로그루브 및 산처리 후 파이브로넥틴을 고정시킨 티타늄시편(E60/10FN) 실험군 제작 후 인간 치은섬유아세포의 세포행동 관련 44개 유전자에 대한 실시간 중합효소연쇄반응 실험을 진행하였다. 결과: 인간치은섬유아세포 부착과 증식 등에 관여하는 4종류 신호전달 경로가 활성화되었다. Focal adhesion 경로에 속하는 Integrin α5, Integrin β1, Integrin β3, Talin-2 유전자들, PI3K-AKT 신호 전달 경로에 속하는 AKT1, AKT2, NF-κB 유전자들, MAPK 신호전달 경로에 속하는 MEK2, ERK1, ERK2 유전자들, 세포주기 신호 전달 경로에 속하는 cyclin D1, CDK4, CDK6 유전자들이 마이크로그루브-파이브로넥틴 복합 티타늄표면(E60/10FN)에서 상향조절되었다. 결론: 마이크로그루브-파이브로넥틴 복합 티타늄표면이 세포행동에 관여하는 다양한 유전자들을 상향조절할 수 있다.

허혈-재관류에 의해 유도된 백혈구-혈관내피세포 유착에 대한 Videomicroscopy 영상소견 (Leukocyte-Endothelial Cell Adhesion Induced by Ischemia and Reperfusion Observed with in vivo Videomicroscopy)

  • 이영배;강한석;박신병
    • Journal of Korean Neurosurgical Society
    • /
    • 제29권10호
    • /
    • pp.1289-1295
    • /
    • 2000
  • Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n=10), and (2)those having the arterial occlusion released after 90 minute(n=20). By 4 hours(n=10) and 24 hours(n=10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n=10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

  • PDF

Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

  • Lee, Kyoung-Jin;Lim, Dongyoung;Yoo, Yeon Ho;Park, Eun-Ji;Lee, Sun-Hee;Yadav, Birendra Kumar;Lee, Yong-Ki;Park, Jeong Hyun;Kim, Daejoong;Park, Kyeong Han;Hahn, Jang-Hee
    • Molecules and Cells
    • /
    • 제39권7호
    • /
    • pp.557-565
    • /
    • 2016
  • The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory $PILR{\alpha}$ and activating $PILR{\beta}$ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit ${\beta}1$ integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of ${\beta}1$ integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of ${\beta}1$ integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.

유전적으로 암호화된 FRET 바이오센서를 통한 세포막 하위 도메인의 Src 활성 비교 분석 (Comparative Analysis of Src Activity in Plasma Membrane Subdomains via Genetically Encoded FRET Biosensors)

  • 최규호;장윤관;서정수;김헌수;안상현;김태진
    • 생명과학회지
    • /
    • 제33권2호
    • /
    • pp.191-198
    • /
    • 2023
  • 세포막의 국소 접착부 복합체에 있는 한 구성원으로써 Src은 비수용체 타이로신 인산화효소 중 하나로 세포부착과 세포 이동성을 조절한다. 그러나 extracellular matrix (ECM)의 구성에 따라 세포막 미세영역에서 어떻게 Src 활성이 조절되는지는 여전히 잘 알려져 있지 않다. 본 연구는 유전적으로 암호화된 FRET 기반 세포막 하위 도메인 표적 Src 바이오센서를 이용해서 3개의 각기 다른 대표적 ECM 단백질인 제1형 콜라겐, 피브로넥틴, 라미닌에 따른 Src의 활성도를 비교 및 조사하였다. FRET 기반 바이오센서는 살아있는 세포에서 단백질의 활성을 시공간적 고해상력을 토대로 실시간으로 분석할 수 있게 해준다. 결과적으로 모든 ECM 조건에서 지질유동섬(Lipid raft)에서 높은 Src 활성을 보였고 ECM 조건에 따라 큰 차이를 보이지 않았다. 반면에 비-지질유동섬(non-Lipid raft)에선 낮은 Src 활성을 보였다. 게다가 같은 ECM 조건일 때 지질유동섬에서 비-지질유동섬보다 높은 Src 활성을 보였다. 따라서 본 연구는 Src 활성이 지질유동섬과 비-지질유동섬에 따라 다르게 조절된다는 것을 보여주었다.

Microarray Data Analysis of Perturbed Pathways in Breast Cancer Tissues

  • Kim, Chang-Sik;Choi, Ji-Won;Yoon, Suk-Joon
    • Genomics & Informatics
    • /
    • 제6권4호
    • /
    • pp.210-222
    • /
    • 2008
  • Due to the polygenic nature of cancer, it is believed that breast cancer is caused by the perturbation of multiple genes and their complex interactions, which contribute to the wide aspects of disease phenotypes. A systems biology approach for the identification of subnetworks of interconnected genes as functional modules is required to understand the complex nature of diseases such as breast cancer. In this study, we apply a 3-step strategy for the interpretation of microarray data, focusing on identifying significantly perturbed metabolic pathways rather than analyzing a large amount of overexpressed and underexpressed individual genes. The selected pathways are considered to be dysregulated functional modules that putatively contribute to the progression of disease. The subnetwork of protein-protein interactions for these dysregulated pathways are constructed for further detailed analysis. We evaluated the method by analyzing microarray datasets of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Using the strategy of microarray analysis, we selected several significantly perturbed pathways that are implicated in the regulation of progression of breast cancers, including the extracellular matrix-receptor interaction pathway and the focal adhesion pathway. Moreover, these selected pathways include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting interesting perturbed pathways that putatively play a role in the progression of breast cancer and provides an improved interpretability of networks of protein-protein interactions.

Weighted Gene Co-expression Network Analysis in Identification of Endometrial Cancer Prognosis Markers

  • Zhu, Xiao-Lu;Ai, Zhi-Hong;Wang, Juan;Xu, Yan-Li;Teng, Yin-Cheng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권9호
    • /
    • pp.4607-4611
    • /
    • 2012
  • Objective: Endometrial cancer (EC) is the most common gynecologic malignancy. Identification of potential biomarkers of EC would be helpful for the detection and monitoring of malignancy, improving clinical outcomes. Methods: The Weighted Gene Co-expression Network Analysis method was used to identify prognostic markers for EC in this study. Moreover, underlying molecular mechanisms were characterized by KEGG pathway enrichment and transcriptional regulation analyses. Results: Seven gene co-expression modules were obtained, but only the turquoise module was positively related with EC stage. Among the genes in the turquoise module, COL5A2 (collagen, type V, alpha 2) could be regulated by PBX (pre-B-cell leukemia homeobox 1)1/2 and HOXB1(homeobox B1) transcription factors to be involved in the focal adhesion pathway; CENP-E (centromere protein E, 312kDa) by E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5 (paired box 5); and BCL-2 (B-cell CLL/lymphoma 2) and IGFBP-6 (insulin-like growth factor binding protein 6) by GLI1. They were predicted to be associated with EC progression via Hedgehog signaling and other cancer related-pathways. Conclusions: These data on transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of EC.

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

  • Cho, Oyeon;Hwang, Hye-Sook;Lee, Bok-Soon;Oh, Young-Taek;Kim, Chul-Ho;Chun, Mison
    • Radiation Oncology Journal
    • /
    • 제33권4호
    • /
    • pp.328-336
    • /
    • 2015
  • Purpose: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

Functional Gene Analysis to Identify Potential Markers Induced by Benzene in Two Different Cell Lines, HepG2 and HL-60

  • Kim, Youn-Jung;Song, Mi-Kyung;Sarma, Sailendra Nath;Choi, Han-Saem;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
    • /
    • 제4권3호
    • /
    • pp.183-191
    • /
    • 2008
  • Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.

조각자(皂角刺)가 estradiol valerate로 유발된 백서(白鼠)의 다낭성 난소에 미치는 영향 (Effects of Gleditsiae Spina(GS) on the Polycystic Ovary Induced by Estradiol Valerate in Rats)

  • 구희준;조성희
    • 대한한방부인과학회지
    • /
    • 제23권2호
    • /
    • pp.71-84
    • /
    • 2010
  • Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

Identifying Differentially Expressed Genes and Screening Small Molecule Drugs for Lapatinib-resistance of Breast Cancer by a Bioinformatics Strategy

  • Zhuo, Wen-Lei;Zhang, Liang;Xie, Qi-Chao;Zhu, Bo;Chen, Zheng-Tang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권24호
    • /
    • pp.10847-10853
    • /
    • 2015
  • Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.