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Levi Todd, Natalie Squires, Lilianna Suarez, Andy J Fischer
Müller glia are capable of de-differentiating and proliferating to become Müller glia-derived progenitor cells (MGPCs) with the ability to regenerate retinal neurons. One of the cell-signaling pathways that drives the reprogramming of Müller glia into MGPCs in the zebrafish retina is the Jak/Stat-pathway. However, nothing is known about the influence of Jak/Stat-signaling during the formation of MGPCs in the retinas of warm-blooded vertebrates. Accordingly, we examined whether Jak/Stat-signaling influences the formation of MGPCs and differentiation of progeny in the avian retina...
October 19, 2016: Scientific Reports
RyeonJin Cho, You-Sun Kim, Ji-Young Kim, Yeon-Mok Oh
BACKGROUND/PURPOSE: Emphysema, a pathologic component of chronic obstructive pulmonary disease, causes irreversible destruction. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. METHODS: We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in elastase-induced emphysema mice. ASCs were administered via an intrapleural route. RESULTS: Mice injected with spheroid ASCs showed improved regeneration of lung tissue, increased expression of growth factors such as FGF2 and HGF, and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs...
October 19, 2016: BMB Reports
Haolin Chen, Yiyan Wang, Renshan Ge, Barry R Zirkin
Adult Leydig cells develop from undifferentiated mesenchymal-like stem cells (stem Leydig cells, SLCs) present in the interstitial compartment of the early postnatal testis. Putative SLCs also have been identified in peritubular and perivascular locations of the adult testis. The latter cells, which normally are quiescent, are capable of regenerating new Leydig cells upon the loss of the adult cells. Recent studies have identified several protein markers to identify these cells, including nestin, PDGFRα, COUP-TFII, CD51 and CD90...
October 12, 2016: Molecular and Cellular Endocrinology
Patience Meo Burt, Liping Xiao, Caroline Dealy, Melanie C Fisher, Marja M Hurley
Humans with X-linked hypophosphatemia (XLH) and Hyp mice, the murine homologue of the disease, develop severe osteoarthropathy and the precise factors that contribute to this joint degeneration remain largely unknown. Fibroblast growth factor 2 (FGF2) is a key regulatory growth factor in osteoarthritis. Although there are multiple FGF2 isoforms the potential involvement of specific FGF2 isoforms in joint degradation has not been investigated. Mice that overexpress the high molecular weight FGF2 isoforms in bone (HMWTg mice) phenocopy Hyp mice and XLH subjects and Hyp mice overexpress the HMWFGF2 isoforms in osteoblasts and osteocytes...
October 12, 2016: Endocrinology
Xiaochu Ding, Jin Gao, Zhouguang Wang, Hassan Awada, Yadong Wang
We designed and tested a versatile hydrogel for tissue regeneration by preserving the bioactivity of growth factors. The shear-thinning gel self-assembles within 1 min from heparin and Laponite-a silicate nanoparticle, thus the name HELP gel. By not covalently modifying heparin, it should retain its natural affinity towards many proteins anchored in the extracellular matrix. In principle, HELP gel can bind any heparin-binding growth factor; we use fibroblast growth factor-2 (FGF2) in this study to demonstrate its utility...
December 2016: Biomaterials
Marta Prieto-Vila, Ting Yan, Anna Sanchez Calle, Neha Nair, Laura Hurley, Tomonari Kasai, Hiroki Kakuta, Junko Masuda, Hiroshi Murakami, Akifumi Mizutani, Masaharu Seno
To grow beyond a size of approximately 1-2 mm(3), tumor cells activate many processes to develop blood vasculature. Growing evidences indicate that the formation of the tumor vascular network is very complex, and is not restricted to angiogenesis. Cancer cell-derived tumor vasculatures have been recently described. Among them, endothelial differentiation of tumor cells have been directly related to cancer stem cells, which are cells within a tumor that possess the capacity to self-renew, and to exhibit multipotential heterogeneous lineages of cancer cells...
2016: American Journal of Cancer Research
Christian Faul
Fibroblast growth factors (FGF) are mitogenic signal mediators that induce cell proliferation and survival. Although cardiac myocytes are post-mitotic, they have been shown to be able to respond to local and circulating FGFs. While precise molecular mechanisms are not well characterized, some FGF family members have been shown to induce cardiac remodeling under physiologic conditions by mediating hypertrophic growth in cardiac myocytes and by promoting angiogenesis, both events leading to increased cardiac function and output...
October 7, 2016: Bone
Deng Pan, Somdutta Roy, Philippe Gascard, Jianxin Zhao, Chira Chen-Tanyolac, Thea D Tlsty
Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit extensive lineage plasticity in vitro and in vivo. Here we visualize these rare ePS cells in a latent state, i.e. lacking SOX2, OCT3/4 and NANOG (SON) expression, in non-diseased breast specimens through immunohistochemical analysis of previously identified ePS-specific biomarkers (CD73(+), EpCAM(+) and CD90(-)). We also report a novel mechanism by which these latent ePS cells acquire SON expression and plasticity in vitro. Four extracellular factors are necessary for the acquisition of SON expression and lineage plasticity in ePS cells: adenosine (which is produced by the 5' ecto-nucleotidase CD73 and activates in turn the PKA-dependent IL6/STAT3 pathway through the adenosine receptor ADORA2b), IL6, FGF2 and ACTIVIN A...
December 2016: Cellular Signalling
Min Tu, Cheng Lu, Nan Lv, Jishu Wei, Zipeng Lu, Chunhua Xi, Jianmin Chen, Feng Guo, Kuirong Jiang, Qiang Li, Junli Wu, Guoxin Song, Shui Wang, Wentao Gao, Yi Miao
Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models...
October 1, 2016: Cancer Letters
G Avallone, V Pellegrino, P Roccabianca, E Lepri, L Crippa, G Beha, L De Tolla, G Sarli
The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP...
October 3, 2016: Veterinary Pathology
Yoav Litvin, Cortney A Turner, Mariel B Rios, Pamela M Maras, Sraboni Chaudhury, Miriam R Baker, Peter Blandino, Stanley J Watson, Huda Akil, Bruce McEwen
We aimed to determine the short-term effects of early-life stress in the form of maternal separation (MS) on anxiety-like behavior in male rat pups. In order to assess anxiety, we measured 40kHz separation-induced ultrasonic vocalizations (USV) on postnatal day (PND) 11. We further aimed to evaluate the potential involvement of two neurochemical systems known to regulate social and anxiety-like behaviors throughout life: oxytocin (OT) and fibroblast growth factor 2 (FGF2). For these purposes, we tested the effects of neonatal administration (on PND1) of an acute dose of FGF2 on USV and its potential interaction with MS...
September 28, 2016: Hormones and Behavior
Elie Traer, Jacqueline Martinez, Nathalie Javidi-Sharifi, Anupriya Agarwal, Jennifer Dunlap, Isabel English, Tibor Kovacsovics, Jeffrey W Tyner, Melissa Wong, Brian J Druker
Potent FLT3 inhibitors such as quizartinib (AC220) have shown promise in treating acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of resistance whereby extrinsic microenvironmental proteins FLT3 ligand (FL) and fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation of ligand-independent resistance mechanisms...
September 26, 2016: Cancer Research
Fanny Ng, Bor Luen Tang
All eukaryotic cells secrete a range of proteins in a constitutive or regulated manner through the conventional or canonical exocytic/secretory pathway characterized by vesicular traffic from the endoplasmic reticulum, through the Golgi apparatus, and towards the plasma membrane. However, a number of proteins are secreted in an unconventional manner, which are insensitive to inhibitors of conventional exocytosis and use a route that bypasses the Golgi apparatus. These include cytosolic proteins such as fibroblast growth factor 2 (FGF2) and interleukin-1β (IL-1β), and membrane proteins that are known to also traverse to the plasma membrane by a conventional process of exocytosis, such as α integrin and the cystic fibrosis transmembrane conductor (CFTR)...
2016: Methods in Molecular Biology
S R Mishra, N Thakur, A Somal, M S Parmar, R Reshma, G Rajesh, V P Yadav, M K Bharti, Jaya Bharati, A Paul, V S Chouhan, G T Sharma, G Singh, M Sarkar
The present study investigated the expression and localization of FGF and its functional receptors in the follicle of buffalo and the treatment of FGF2 on mRNA expression of CYP19A1 (aromatase), PCNA, and BAX (BCL-2 associated X protein) in cultured buffalo granulosa cells (GCs). Follicles were classified into four groups based on size and E2 level in follicular fluid (FF): F1, 4-6mm diameter, E2<0.5ng/ml of FF; F2, 7-9mm, E2=0.5-5ng/ml; F3, 10-13mm, E2=5-40ng/ml; F4, >14mm, E2>180ng/ml. The qPCR studies revealed that the mRNA expression of FGF1, FGF2 and FGF7 were maximum (P<0...
October 2016: Research in Veterinary Science
Paula Pierozan, Helena Biasibetti, Felipe Schmitz, Helena Ávila, Mariana M Parisi, Florencia Barbe-Tuana, Angela T S Wyse, Regina Pessoa-Pureur
QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling...
September 20, 2016: Biochimica et Biophysica Acta
Christina L O'Neill, Jasenka Guduric-Fuchs, Sarah Ej Chambers, Michelle O'Doherty, Barbara Bottazzi, Alan W Stitt, Reinhold J Medina
AIMS: Circulating Angiogenic Cells (CACs) promote revascularization of ischemic tissues although their underlying mechanism of action and the consequences of delivering varying numbers of these cells for therapy remain unknown. This study investigates molecular mechanisms underpinning CAC modulation of blood vessel formation. METHODS & RESULTS: CACs at low (2x10(5)cells/ml) and mid (2x10(6)cells/ml) cellular densities significantly enhanced endothelial cell (EC) tube formation in vitro, while high density CACs (2x10(7)cells/ml) significantly inhibited this angiogenic process...
September 22, 2016: Cardiovascular Research
Masaki Takahashi, Masashi Fukuoka, Katsuji Yoshioka, Hirohiko Hohjoh
Acquired drug resistance is a major problem in chemotherapy, and understanding of the mechanism, by which naïve cells defend themselves from drugs when the cells exposed to the drugs for the first time, may provide a solution of the problem. Gefitinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and used as an anticancer drug; however, gefitinib treatment may sometimes lead cancer cells gradually into a gefitinib-tolerance. Here we describe that human adenocarcinoma PC-9 cells even under the presence of gefitinib were able to survive by activating another signaling pathway involving fibroblast growth factor receptor (FGFR) and its signaling molecule, FGF2; and further suggest that the FGF2 for initiating the pathway might be supplied from neighboring cells which were killed by gefitinib, i...
October 14, 2016: Biochemical and Biophysical Research Communications
Jin Nishino, Miwa Yamazaki, Masanobu Kawai, Kanako Tachikawa, Keiko Yamamoto, Kazuaki Miyagawa, Mikihiko Kogo, Keiichi Ozono, Toshimi Michigami
Dentin matrix protein 1 (DMP1) is an extracellular matrix protein involved in phosphate metabolism and biomineralization, and its expression markedly increases during the maturation of osteoblasts into osteocytes. We previously reported that an increased level of inorganic phosphate (Pi) in media up-regulated the expression of Dmp1 in primary osteocytes isolated from mouse bones. In the present study, we found that elevated extracellular Pi strongly induced the expression of Dmp1 in osteoblasts and explored its underlying mechanism of action...
September 17, 2016: Journal of Cellular Biochemistry
Constantino Tomas-Sanchez, Victor Manuel Blanco-Alvarez, Juan Antonio Gonzalez-Barrios, Daniel Martinez-Fong, Guadalupe Garcia-Robles, Guadalupe Soto-Rodriguez, Eduardo Brambila, Maricela Torres-Soto, Alejandro Gonzalez-Vazquez, Ana Karina Aguilar-Peralta, José-Luis Garate-Morales, Luis-Angel Aguilar-Carrasco, Daniel I Limón, Jorge Cebada, Bertha Alicia Leon-Chavez
Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points...
2016: Journal of Immunology Research
Cinzia Cocola, Stefano Molgora, Maria Cristina Veronesi, Marianna Greco, Cinzia Bragato, Monica Moro, Mariacristina Crosti, Brian Gray, Luciano Milanesi, Valeria Grieco, Gaia Cecilia Luvoni, James Kehler, Gianfranco Bellipanni, Rolland Reinbold, Ileana Zucchi, Antonio Giordano
Recent studies suggest that human tumors are generated from cancer cells with stem cell (SC) properties. Spontaneously occurring cancers in dogs contain a diversity of cells that like for human tumors suggest that certain canine tumors are also generated from cancer stem cells (CSCs). CSCs, like normal SCs have the capacity for self-renewal as mammospheres in suspension cultures. To understand how cells with SC properties contribute to canine mammary gland tumor development and progression, comparative analysis between normal SCs and CSCs, obtained from the same individual is essential...
September 15, 2016: Journal of Cellular Biochemistry
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