• BMB Reports
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• 제46권5호
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• pp.276-281
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• 2013

In this study, we aimed to compare the morphogenetic and neuronal characteristics between monolayer cells and spheroids. For this purpose, we established spheroid formation by growing SH-SY5Y cells on the hydrophobic surfaces of thermally-collapsed elastin-like polypeptide. After 4 days of culture, the relative proliferation of the cells within spheroids was approximately 92% of the values for monolayer cultures. As measured by quantitative assays for mRNA and protein expressions, the production of synaptophysin and neuronspecific enolase (NSE) as well as the contents of cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins are much higher in spheroids than in monolayer cells. Under the all-trans-retinoic acid (RA)-induced differentiation condition, spheroids extended neurites and further up-regulated the expression of synaptophysin, NSE, CAMs, and ECM proteins. Our data indicate that RA-differentiated SH-SY5Y neurospheroids are functionally matured neuronal architectures.

• Macromolecular Research
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• 제15권4호
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• pp.370-378
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• 2007

Mechanical stimulation is known to activate several cellular signal transduction pathways, leading to the induction of signaling molecules and extracellular matrix (ECM) proteins, thereby modulating cellular activities, such as proliferation and survival. In this study, primary human dermal fibroblasts (HDFs) were seeded onto chitosan-based scaffolds, and then cultured for 3 weeks in a bioreactor under a cyclic strain of 1 Hz frequency. Compared to control samples cultured under static conditions, the application of a cyclic strain stimulated the proliferation of HDFs in I week, and by week 3 the thickness of the cell/scaffold composites increased 1.56 fold. Moreover, immunohistochemical staining of the culture media obtained from the cell/scaffold samples subjected to the cyclic strain, revealed increases in the expression and secretion of ECM proteins, such as fibronectin and collagen. These results suggest that the preconditioning of cell/scaffold composites with a cyclic strain may enhance the proliferation of HDFs, and even facilitate integration of the engineered artificial dermal tissue into the host graft site.

• Clinical and Experimental Reproductive Medicine
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• 제48권4호
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• pp.303-310
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• 2021

Decorin (DCN) is a proteoglycan belonging to the small leucine-rich proteoglycan family. It is composed of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate. DCN is a structural component of connective tissues that can bind to type I collagen. It plays a role in the assembly of the extracellular matrix (ECM), and it is related to fibrillogenesis. It can interact with fibronectin, thrombospondin, complement component C1, transforming growth factor (TGF), and epidermal growth factor receptor. Normal DCN expression regulates a wide range of cellular processes, including proliferation, migration, apoptosis, and autophagy, through interactions with various molecules. However, its aberrant expression is associated with oocyte maturation, oocyte quality, and poor extravillous trophoblast invasion of the uterus, which underlies the occurrence of preeclampsia and intrauterine growth restriction. Spatiotemporal hormonal control of successful pregnancy should regulate the concentration and activity of specific proteins such as proteoglycan participating in the ECM remodeling of trophoblastic and uterine cells in fetal membranes and uterus. At the human feto-maternal interface, TGF-β and DCN play crucial roles in the regulation of trophoblast invasion of the uterus. This review summarizes the role of the proteoglycan DCN as an important and multifunctional molecule in the physiological regulation of oocyte maturation and trophoblast migration. This review also shows that recombinant DCN proteins might be useful for substantiating diverse functions in both animal and in vitro models of oogenesis and implantation.

• 대한화장품학회지
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• 제33권4호
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• pp.245-249
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• 2007

노화 과정 중에 일어나는 extracellular matrix (ECM)의 변성은 피부의 주름과 탄력 감소를 유발한다. 현재까지 항노화의 주요 타겟은 metalloproteases 혹은 콜라겐이나 엘라스틴 같은 구조 단백질에 집중되어 있지만, 최근 세포와 ECM 단백질(콜라겐, 피브릴린, 파이브로넥틴) 간의 상호작용이 세포의 생존과 증식, 조직의 재건에 중요한 역할을 한다고 알려졌다. 파이브로넥틴은 다른 ECM 단백질이나 인테그린 같은 세포 표면 수용체와 결합할 수 있는 부위를 가진 부착 단백질이다. 최근 보고에 따르면 세린 프로티아제들에 의해 분해된 파이프로넥틴 조각이 골아세포에서 MMPs 발현을 증가시킨다. 그러나 파이브로넥틴 조각의 사람 피부에서의 역할은 보고된 바 없다. 본 연구에서는 노인의 피부에서 파이브로넥틴 조각이 현저히 증가되어 있으며, 섬유아세포에 파이브로넥틴 조각을 처리하였을 시, MMP-1의 발현과 MMP-2의 활성이 증가한다는 것을 입증하였다. 이 결과는 파이브로넥틴 조각이 피부 노화를 유발하는 새로운 인자일 가능성을 제시하고 있다.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.288-292
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• 2009

Interactions between tumor cells and the extracellular matrix (ECM) strongly influence tumor development, affecting cell survival, proliferation and migration. Fibronectin, a major component of ECM, has been shown to interact with integrins especially the ${\alpha}5{\beta}1$ integrin. Cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs) which are capable of digesting the different components of the ECM and basement membrane. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated, resulting the 62 kDa active MMP-2. In this study, we investigated the effect of fibronectin on activation of pro-MMP-2 and the cellular invasiveness in H-Ras-transformed MCF10A human breast epithelial cells. Here we show that fibronectin induces activation of pro-MMP-2 and up-regulation of MT1-MMP and TIMP-2 in H-Ras MCF10A cells. These results demonstrate that H-Ras MCF10A cells secrete high levels of active MMP-2 when cultured with fibronectin, suggesting a possible interaction between the ECM network and H-Ras MCF10A cells to generate active MMP-2 which is important for proteolysis and ECM remodeling. Invasive and migratory abilities of H-Ras MCF10A cells were enhanced by fibronectin. Fibronectin up-regulated the expression of ${\beta}1$ integrin which may play a role in cellular responses exerted by fibronectin. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, this study provides a mechanism for the cell surface-matrix degrading effect of fibronectin which will be crucial to breast cell invasion and migration.

• Journal of Periodontal and Implant Science
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• 제47권6호
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• pp.363-371
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• 2017

Purpose: The purpose of this study was to investigate the feasibility of regenerative therapy with a collagenated bone graft and resorbable membrane in intrabony defects, and to evaluate the effects of the novel extracellular matrix (ECM)-based membrane clinically and radiologically. Methods: Periodontal tissue regeneration procedure was performed using an ECM-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects around the teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used membrane (WEM) were randomly applied to the test group and the control group, respectively. Cone-beam computed tomography images were obtained on the day of surgery and 6 months after the procedure. Alginate impressions were taken and plaster models were made 1 week and 6 months postoperatively. Results: The quantity of bone tissue, the dimensional changes of the surgically treated intrabony defects, and the changes in width and height below the grafted bone substitutes showed no significant difference between the test and control groups at the 6-month examination. Conclusions: The use of NEM for periodontal regeneration with a collagenated bovine bone graft showed similar clinical and radiologic results to those obtained using WEM.

• 생명과학회지
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• 제32권2호
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• pp.175-188
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• 2022

혈관과 섬유증 기관들의 평활근과 세포외기질에 대한 릴랙신의 조절기능이 입증되어왔다. 본 총설에서는 저항성 소동맥과 방광을 포함한 섬유증 기관들의 세포외기질에 작용하는 릴랙신의 다양한 기전들을 고찰한다. 릴랙신은 혈관 평활근육의 수축을 억제하고, 콜라겐과 같은 세포외기질의 구성성분들을 감소키켜 혈관벽의 수동적 신전성을 증가시킴으로써, 혈관확장을 유도한다. 릴랙신이 동맥의 혈관확장을 유도하는 주된 세포기전은 RXFP1/PI3K의 활성화, Akt 인산화 및 eNOS 활성화를 통한 내피세포-의존성 산화질소의 생성에 의해 매개된다. 추가적으로, 릴랙신은 또한 다른 대체경로들을 작동하여 신장과 장간막 동맥의 혈관확장을 증가시킨다. 신장 소동맥에서, 릴랙신은 내피세포의 MMPs 및 EtB 수용체의 활성화와 VEGF 및 PlGF의 생성을 촉진하여, 평활근의 수축성과 콜라겐의 침착을 억제함으로써 혈관확장을 초래한다. 이와 달리, 장간막 소동맥에서, 릴랙신은 bradykinin (BK)-유도 이완을 시간-의존적으로 증강시킨다. BK-매개 이완의 신속 증가는 IK_Ca 이온통로와 뒤이은 EDH 유발에 의존하는 반면, BK에 의한 지속적 이완은 COX 활성과 PGI₂에 의존한다. 릴랙신의 항섬유화 효과는 염증유발 면역세포의 침투, endothelial-to-mesenchymal transition (EndMT) 및 근섬유아세포의 분화와 활성을 억제하여 매개된다. 릴랙신은 또한 근섬유아세포 내 NOS/NO/cGMP/PKG-1 경로를 활성화하여, TGF-β1-유도 ERK1/2 및 Smad2/3 신호의 활성과 ECM 콜라겐의 침착을 억제한다.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.281-290
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• 2024

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.

• 한국표면공학회:학술대회논문집
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• 한국표면공학회 2013년도 춘계학술대회 논문집
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• pp.38-38
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• 2013

The mechanical cues that adherent cells derive from the extracellular matrix (ECM) can effect dramatic changes in cell migration, proliferation, and differentiation. Using a thin film of Type I collagen fibrils comprised of 100 nm to 200 nm collagen fibrils overlaying a bed of smaller fibrils, changes in cellular response to systematically controlled changes in mechanical properties of collagen was investigated. Further, an experimental and modeling approaches to calculate the elastic modulus of individual collagen fibrils, and thereby the effective stiffness of the entire collagen thin film matrix, from atomic force microscopy force spectroscopy data was performed. These results demonstrate an approach to analysis of fundamental properties of thin, heterogeneous, organic films, and add further insights into the mechanical properties of collagen fibrils that are of relevance to cell response to the ECM.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2000년도 추계학술대회 및 정기총회
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• pp.30-30
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• 2000

Hepatic fibrosis/cirrhosis is characterized by increased production and deposition of collagen, noncollagenous glycaproteins, and proteoglycans, which mainly compose the extracellular matrix (ECM). Recently, activations of macrophages, myofibroblasts and mast cells are thaught ta be associated with the accumulation of ECM. In order to investigate the kinetics of macrophages, myofibroblasts and mast cells and the relationship between these cells and the accumulation of ECM in carban tetrachloride (CCl$_4$)-injected rat liver, we induced liver cirrhosis of rat by an injection of CCl$_4$ for 14 weeks. (omitted)