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Jingyu Jin, Sharada Tilve, Zhonghai Huang, Libing Zhou, Herbert M Geller, Panpan Yu
As one major component of extracellular matrix (ECM) in the central nervous system, chondroitin sulfate proteoglycans (CSPGs) have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite outgrowth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron (CGN) culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, including cell adhesion, spreading and neurite growth...
February 2018: Neural Regeneration Research
Arash Mehdizadeh, Bruce S Gardiner, Michael Lavagnino, David W Smith
The composition of extracellular matrix (ECM) in tendon depends on the secretion profile of resident cells known as tenocytes. For tissues with a mechanical role like tendon, mechanical strain is known to play an important role in determining the secretion profile of resident cells. Previously we explored the idea of estimating average concentrations of ECM molecules as a function of tendon strain magnitude and number of loading cycles. Specifically, we developed a model of the mechanical fatigue damage of tendon collagen fibers and introduced elementary cell responses (ECRs) by which local cellular-level responses to the strain environment, combined with the fatigue damage model, were scaled up to predict tissue-level responses...
March 20, 2018: Connective Tissue Research
Boju Pan, Junchao Guo, Quan Liao, Yupei Zhao
Integrins are transmembrane glycoproteins that consist of an α and a β subunit. Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins to affect the characteristics of cells or the components of the ECM. Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different cancer-associated processes, including the initiation, proliferation, survival, migration and invasion. Furthermore, previous studies have revealed a ratio between these two integrins in cancer cells, which also demonstrated that the functions of these two integrins are paradoxical...
April 2018: Oncology Letters
Tong Zhu, Xueqian Hu, Pinkang Wei, Guangzhi Shan
Gastric cancer (GC) is one of the deadliest types of cancer in the world. Lymph node (LN) metastasis is a complex and malignant behavior of GC, involving a sequence of biological processes, including decreased adherence to adjacent cells, extracellular matrix (ECM) degradation and lymphatic channel permeation. LN metastasis is directly associated with the treatment response, local recurrence and long-term survival of patients with GC. Therefore, the molecular mechanisms of LN metastasis in GC development require further investigation...
March 2018: Oncology Letters
Hui Cao, Senlin Li, Rui Xie, Na Xu, Ying Qian, Hongdan Chen, Qinyu Hu, Yihong Quan, Zhihong Yu, Junjun Liu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB)...
2018: Frontiers in Pharmacology
Wei-Dong Lü, Rui-Fang Sun, Ye-Rong Hu, Jan-Rong Lu, Lu Gu, Zhi-Gang Liu, Guang-Yan Lei, Zhun Qiang, Lin Cai
Acellular tumor extracellular matrices (ECMs) have limitations when employed as three-dimensional scaffolds for tumor engineering. In this work, methylene blue-mediated photooxidation was used to crosslink acellular tumor ECMs. Photooxidative crosslinking greatly increased the stiffness of acellular tumor ECM scaffolds but barely altered the Amide III band of the secondary structure of polypeptides and proteins. MCF-7, HepG2 and A549 cells cultured on photooxidatively crosslinked acellular tumor ECM scaffolds exhibited greater cell number per scaffold, more IL-8 and VEGF secretion, and increase migration and invasion abilities than cells cultured on uncrosslinked acellular tumor ECM scaffolds...
March 16, 2018: Acta Biomaterialia
Qing Li, Chao Wang, Biao Han, Feini Qu, Hao Qi, Christopher Y Li, Robert L Mauck, Lin Han
To elucidate how maturation impacts the structure and mechanics of meniscus extracellular matrix (ECM) at the length scale of collagen fibrils and fibers, we tested the micromechanical properties of fetal and adult bovine menisci via atomic force microscopy (AFM)-nanoindentation. For circumferential fibers, we detected significant increase in the effective indentation modulus, Eind , with age. Such impact is in agreement with the increase in collagen fibril diameter and alignment during maturation, and is more pronounced in the outer zone, where collagen fibrils are more aligned and packed...
March 9, 2018: Journal of Biomechanics
Lisa A Sawicki, Leila H Choe, Katherine L Wiley, Kelvin H Lee, April M Kloxin
Cells interact with and remodel their microenvironment, degrading large extracellular matrix (ECM) proteins (e.g., fibronectin, collagens) and secreting new ECM proteins and small soluble factors (e.g., growth factors, cytokines). Synthetic mimics of the ECM have been developed as controlled cell culture platforms for use in both fundamental and applied studies. However, how cells broadly remodel these initially well-defined matrices remains poorly understood and difficult to probe. In this work, we have established methods for widely examining both large and small proteins that are secreted by cells within synthetic matrices...
March 12, 2018: ACS Biomaterials Science & Engineering
Chengliang Zhang, Yanfeng Zhang, Hong Zhu, Jiajia Hu, Zhongshang Xie
Cardiac fibrosis is associated with diverse heart diseases. In response to different pathological irritants, cardiac fibroblasts may be induced to proliferate and differentiate into cardiac myofibroblasts, thus contributing to cardiac fibrosis. TGF-β signaling is implicated in the development of heart failure through the induction of cardiac fibrosis. C-Ski, an inhibitory regulator of TGF-β signaling, has been reported to suppress TGF-β1-induced human cardiac fibroblasts' proliferation and ECM protein increase; however, the underlying molecular mechanism needs further investigation...
March 15, 2018: Cellular Signalling
Jifang Ma, Lei Zhang, Jianbing Hao, Naqi Li, Jie Tang, Lirong Hao
TGF-β1-induced excessive deposition of ECM and EMT process of tubular epithelial cells play critical roles in the development and progression of fibrosis in diabetic nephropathy (DN). Orai1 has been demonstrated to be involved in TGF-β1-induced EMT via TGF-β/Smad3 pathway. We are aimed to explore the effects of miR-93 on TGF-β1-induced EMT process in HK2 cells. In this study, our data showed that miR-93 was dramatically decreased in renal tissues of patients with DN and TGF-β1-stimulated HK2 cells. Moreover, the decreased level of miR-93 was closely associated with the increased expression of Orai1...
February 14, 2018: Journal of Pharmacological Sciences
Beyza Gökçinar-Yagci, Nilgün Yersal, Petek Korkusuz, Betül Çelebi-Saltik
Small-diameter vascular grafts are needed for the treatment of coronary artery diseases in the case of limited accessibility of the autologous vessels. Synthetic scaffolds have many disadvantages so in recent years vascular constructs (VCs) made from cellularized natural scaffolds was seen to be very promising but number of studies comprising this area is very limited. In our study, our aim is to generate fully natural triple-layered VC that constitutes all the layers of blood vessel with vascular cells. CD146+ perivascular cells (PCs) were isolated from human umbilical cord vein (HUCV) and differentiated into smooth muscle cells (SMCs) and fibroblasts...
March 14, 2018: Microvascular Research
Christophe O Chantre, Patrick H Campbell, Holly M Golecki, Adrian T Buganza, Andrew K Capulli, Leila F Deravi, Stephanie Dauth, Sean P Sheehy, Jeffrey A Paten, Karl Gledhill, Yanne S Doucet, Hasan E Abaci, Seungkuk Ahn, Benjamin D Pope, Jeffrey W Ruberti, Simon P Hoerstrup, Angela M Christiano, Kevin Kit Parker
Wounds in the fetus can heal without scarring. Consequently, biomaterials that attempt to recapitulate the biophysical and biochemical properties of fetal skin have emerged as promising pro-regenerative strategies. The extracellular matrix (ECM) protein fibronectin (Fn) in particular is believed to play a crucial role in directing this regenerative phenotype. Accordingly, Fn has been implicated in numerous wound healing studies, yet remains untested in its fibrillar conformation as found in fetal skin. Here, we show that high extensional (∼1...
March 5, 2018: Biomaterials
Xiaojing Huang, Hongwen Zhu, Zemin Gao, Junzun Li, Junlong Zhuang, Yu Dong, Bing Shen, Meiqian Li, Hu Zhou, Hongqian Guo, Ruimin Huang, Jun Yan
Once urinary bladder cancer (UBC) develops into muscle-invasive bladder cancer, its mortality rate increases dramatically. However, the molecular mechanisms of UBC invasion and metastasis remain largely unknown. Herein, using 5637 UBC cells, we generated two sublines with low (5637 NMI) and high (5637 HMI) invasive capabilities. Mass spectrum analyses revealed that the Wnt family protein Wnt7a is more highly expressed in 5637 HMI cells than in 5637 NMI cells. We also found that increased Wnt7a expression is associated with UBC metastasis and predicted worse clinical outcome in UBC patients...
March 16, 2018: Journal of Biological Chemistry
Maria Emilia Isolani, Renata Batistoni, Chiara Ippolito, Anna Maria Bianucci, Silvia Marracci, Leonardo Rossi
Planarian flatworms possess extraordinary regenerative capability and body plasticity, which rely on a composite population of stem cells, the neoblasts. Despite impressive advances have been recently achieved in the knowledge of neoblast biology, few is still known about factors that are released by differentiated tissues and influence the neoblast fate. Extracellular matrix (ECM) is a fundamental component of the stem cell niche and its remodeling affects stem cell fate. Here we provide the characterization of the astacin gene family of metalloproteinases in planarians, good candidate enzymes for generating dynamicity in the ECM...
March 13, 2018: Gene Expression Patterns: GEP
Eva Jover, Ana Silvente, Francisco Marín, José Martínez-González, Mar Orriols, Carlos M Martinez, Carmen María Puche, Mariano Valdés, Cristina Rodriguez, Diana Hernández-Romero
Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia (HPM)-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by HPM conditioning...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Mateusz M Urbanski, Carmen V Melendez-Vasquez
Extracellular matrix (ECM) elasticity may direct cellular differentiation and can be modeled in vitro using synthetic ECM-like substrates with defined elastic properties. However, the effectiveness of such approaches depends on the selection of a range of elasticity and ECM ligands that accurately model the relevant tissue. Here, we present a cell culture system than can be used to study Schwann cell differentiation on substrates which model the changes in mechanical ECM properties that occur during sciatic nerve development...
2018: Methods in Molecular Biology
Mark Owyong, Gizem Efe, Michael Owyong, Aamna J Abbasi, Vaishnavi Sitarama, Vicki Plaks
There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy...
2018: Frontiers in Cell and Developmental Biology
Marija Adzic, Nadezda Nedeljkovic
CD73 is a bifunctional glycosylphosphatidylinositol (GPI)-anchored membrane protein which functions as ecto-5'-nucleotidase and a membrane receptor for extracellular matrix protein (ECM). A large body of evidence demonstrates a critical involvement of altered purine metabolism and particularly, increased expression of CD73 in a number of human disorders, including cancer and immunodeficiency. Massive up-regulation of CD73 was also found in reactive astrocytes in several experimental models of human neuropathologies...
2018: Frontiers in Pharmacology
IlKyoo Koh, Junghwa Cha, Junseong Park, Junjeong Choi, Seok-Gu Kang, Pilnam Kim
Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion...
March 15, 2018: Scientific Reports
Thais Assis-Ribas, Maria Fernanda Forni, Sheila Maria Brochado Winnischofer, Mari Cleide Sogayar, Marina Trombetta-Lima
Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance...
March 12, 2018: Developmental Biology
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