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https://www.readbyqxmd.com/read/29353205/wisp3-prevents-fibroblast-myofibroblast-transdifferentiation-in-nrk-49f-cells
#1
Yang Yi, Jun Ma, Lu Jianrao, Hangqing Wang, Yingdan Zhao
CCN family, a group of six extracellular matrix-associated proteins, plays an important role in fibrosis. WISP3 has addressed as a pro-fibrotic molecule in the development of human lung fibrosis. However, whether WISP3 involved in the activation and proliferation of renal fibroblast, and ultimately inhibited fibroblast-myofibroblast transdifferentiation remained unknown. Herein, we found that down-regulated WISP3 was involved in the fibrogenesis of rat renal NRK-49F cells induced by transforming growth (TGF-β1), which was further confirmed in a rat renal fibrosis induced by unilateral ureteral obstruction (UUO)...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29353044/bmp4-signaling-in-npcs-upregulates-bcl-xl-to-promote-their-survival-in-the-presence-of-fgf-2
#2
Hanako Yamamoto, Masashi Kurachi, Masae Naruse, Koji Shibasaki, Yasuki Ishizaki
We previously reported that BMP4 does not promote proliferation or differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In this study, we examined if BMP4 acts as a survival factor also for neural stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse brain. We found BMP4 promotes survival but not proliferation or differentiation of these cells, just as in the case for CD44-positive APCs...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29351855/the-relationship-of-circulating-fibroblast-growth-factor-21-levels-with-incident-atrial-fibrillation-the-multi-ethnic-study-of-atherosclerosis
#3
Tsz Him Hui, Robyn L McClelland, Matthew A Allison, Carlos J Rodriguez, Richard A Kronmal, Susan R Heckbert, Erin D Michos, Philip J Barter, Kerry-Anne Rye, Kwok Leung Ong
BACKGROUND AND AIMS: Elevated circulating levels of fibroblast growth factor 21 (FGF21) are associated with multiple cardiovascular disease (CVD) risk factors and incident events. Previous small cross-sectional studies, mainly in Chinese populations, have suggested FGF21 may play a role in the development of atrial fibrillation (AF). We therefore investigated the relationship of FGF21 levels with incident AF in participants free of clinically apparent CVD at baseline in a large, multi-ethnic cohort...
December 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29351845/a-precise-cdk-activity-threshold-determines-passage-through-the-restriction-point
#4
Clayton Schwarz, Amy Johnson, Mardo Kõivomägi, Evgeny Zatulovskiy, Carolyn J Kravitz, Andreas Doncic, Jan M Skotheim
At the restriction point (R), mammalian cells irreversibly commit to divide. R has been viewed as a point in G1 that is passed when growth factor signaling initiates a positive feedback loop of Cdk activity. However, recent studies have cast doubt on this model by claiming R occurs prior to positive feedback activation in G1 or even before completion of the previous cell cycle. Here we reconcile these results and show that whereas many commonly used cell lines do not exhibit a G1 R, primary fibroblasts have a G1 R that is defined by a precise Cdk activity threshold and the activation of cell-cycle-dependent transcription...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351444/activated-human-t-lymphocytes-inhibit-tgf%C3%AE-induced-fibroblast-to-myofibroblast-differentiation-via-prostaglandins-d2-and-e2
#5
Shannon H Lacy, Amali P Epa, Stephen J Pollock, Collynn F Woeller, Thomas H Thatcher, Richard P Phipps, Patricia J Sime
In pulmonary fibrosis (PF), fibroblasts and myofibroblasts proliferate and deposit excessive extracellular matrix in the interstitium, impairing normal lung function. As most forms of PF have a poor prognosis and limited treatment options, PF represents an urgent unmet need for novel, effective therapeutics. While the role of immune cells in lung fibrosis is unclear, recent studies suggest that T lymphocyte (T cell) activation may be impaired in PF patients. Further, we have previously shown that activated T cells can produce prostaglandins with anti-scarring potential...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351434/cub-domain-containing-protein-1-cdcp1-negatively-regulates-tgf%C3%AE-signaling-and-myofibroblast-differentiation
#6
Nina Noskovičová, Katharina Heinzelmann, Gerald Burgstaller, Jürgen Behr, Oliver Eickelberg
Fibroblasts are thought to be the prime cell type for producing and secreting extracellular matrix (ECM) proteins in the connective tissue. The profibrotic cytokine, transforming growth factor-beta 1 (TGFβ1) activates and transdifferentiates fibroblasts into αSMA-expressing myofibroblasts, which exhibit increased ECM secretion, in particular collagens. Little information, however, exists about cell-surface molecules on fibroblasts that mediate this transdifferentiation process. We recently identified, using unbiased cell-surface proteome analysis, Cub domain containing protein 1 (CDCP1) to be strongly downregulated by TGFβ1...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351412/expression-of-ctgf-ccn2-in-response-to-lpa-is-stimulated-by-fibrotic-extracellular-matrix-via-the-integrin-fak-axis
#7
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351293/fibroblast-growth-factor-receptor-1-amplification-in-laryngeal-squamous-cell-carcinoma
#8
Jesus Monico, Brandon Miller, Luminita Rezeanu, Warren May, Donna C Sullivan
Fibroblast growth factor receptor 1 (FGFR1) has been noted to be amplified in a variety of squamous cell carcinomas (SCCa) of the head, neck, and lung and increased copy number (CN) is a predictor of poor outcomes. FGFR1 is a therapeutic target for lung SCCa and inhibition therapy is currently in clinical trials. Absolute quantification of FGFR1 from formalin fixed paraffin embedded (FFPE) tissue of laryngeal SCCa was examined in this retrospective study. A droplet digital polymerase chain reaction (ddPCR) was used for absolute quantitation of the FGFR1 gene CN...
2018: PloS One
https://www.readbyqxmd.com/read/29351058/development-and-characterization-of-an-in-vitro-model-for-radiation-induced-fibrosis
#9
Dhruv Kumar, Sreeya Yalamanchali, Jacob New, Sean Parsel, Natalie New, Andrew Holcomb, Sumedha Gunewardena, Ossama Tawfik, Chris Lominska, Bruce F Kimler, Shrikant Anant, Kiran Kakarala, Terance Tsue, Yelizaveta Shnayder, Kevin Sykes, Subhash Padhye, Sufi Mary Thomas
Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in tissues and organ failure. Development of preclinical models of RIF is crucial to elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic approaches. In addition to radiation, the main molecular perpetrators of fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β)...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29351036/crouzon-with-acanthosis-nigricans-and-odontogenic-tumors-a-rare-form-of-syndromic-craniosynostosis
#10
Wen Xu, Donna M McDonald-McGinn, Alexandra J Melchiorre, Elaine H Zackai, Scott P Bartlett, Jesse A Taylor
Crouzon syndrome with acanthosis nigricans (CAN) is caused by a mutation in the fibroblast growth factor receptor ( FGFR) 3 gene that presents clinically as Crouzonoid craniofacial features in association with other anomalies such as acanthosis nigricans and benign odontogenic tumors. Diagnosis through the use of genetic mutational analysis is critical, as it alerts the surgeon to the need for careful screening for jaw tumors so that timely treatment in the form of curettage or segmental resection can be provided...
February 2018: Cleft Palate-craniofacial Journal
https://www.readbyqxmd.com/read/29349588/amphiregulin-enhances-cardiac-fibrosis-and-aggravates-cardiac-dysfunction-in-mice-with-experimental-myocardial-infarction-partly-through-activating-egfr-dependent-pathway
#11
Liang Liu, Xian Jin, Cui-Fen Hu, Ya-Ping Zhang, Zhong'e Zhou, Rong Li, Cheng-Xing Shen
Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts...
January 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29349300/tensile-forces-drive-a-reversible-fibroblast-to-myofibroblast-transition-during-tissue-growth-in-engineered-clefts
#12
Philip Kollmannsberger, Cécile M Bidan, John W C Dunlop, Peter Fratzl, Viola Vogel
Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor-β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29348826/interaction-of-macrophages-with-apoptotic-cells-inhibits-transdifferentiation-and-invasion-of-lung-fibroblasts
#13
Yong-Bae Kim, Young-So Yoon, Youn-Hee Choi, Eun-Mi Park, Jihee Lee Kang
The invasion of activated fibroblasts is a key mechanism of tissue fibrosis pathology. The recognition and uptake of apoptotic cells can induce the anti-fibrogenic programming of macrophages. We demonstrate that after interacting with apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF-β1-induced increases in myofibroblast (fibroproliferative) phenotypic markers and reduce the enhanced invasive capacity of TGF-β1- or EGF-treated mouse lung fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti-fibrotic effects of conditioned media, including transfection of macrophages with COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for prostaglandin E2 (PGE2), PGD2, or hepatocyte growth factor (HGF)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348470/fibroblast-growth-factor-21-increases-insulin-sensitivity-through-specific-expansion-of-subcutaneous-fat
#14
Huating Li, Guangyu Wu, Qichen Fang, Mingliang Zhang, Xiaoyan Hui, Bin Sheng, Liang Wu, Yuqian Bao, Peng Li, Aimin Xu, Weiping Jia
Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are well-documented, uncertainty about its role in regulating excessive energy intake remains. Here, we show that FGF21 improves systemic insulin sensitivity by promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21 levels positively correlate with the SAT area in insulin-sensitive obese individuals. FGF21 knockout mice (FGF21KO) show less SAT mass and are more insulin-resistant when fed a high-fat diet. Replenishment of recombinant FGF21 to a level equivalent to that in obesity restores SAT mass and reverses insulin resistance in FGF21KO, but not in adipose-specific βklotho knockout mice...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348469/treprostinil-inhibits-proliferation-and-extracellular-matrix-deposition-by-fibroblasts-through-camp-activation
#15
Christopher Lambers, Michael Roth, Peter Jaksch, Gabriella Muraközy, Michael Tamm, Walter Klepetko, Bahil Ghanim, Feng Zhao
Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-β1, or the combination...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29344510/ablation-of-fgfr2-in-fibroblasts-ameliorates-kidney-fibrosis-after-ischemia-reperfusion-injury-in-mice
#16
Zhuo Xu, Chunsun Dai
Background: Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation. Methods: In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29344330/developments-in-rare-bone-diseases-and-mineral-disorders
#17
REVIEW
Siobhan Bacon, Rachel Crowley
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29344235/metronomic-chemotherapy-remodel-cancer-associated-fibroblasts-to-decrease-chemoresistance-of-gastric-cancer-in-nude-mice
#18
Chao Wang, Wenqi Xi, Jinling Jiang, Jun Ji, Yingyan Yu, Zhenggang Zhu, Jun Zhang
The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu) chemotherapy with the metronomic pattern may cause significant chemoresistance compared with the traditional pattern, and whether CAFs are involved in drug resistance. SGC-7901 cells were subcutaneously injected into the nude mice, and the mice were divided into five groups: The control group, intraperitoneally injected with normal saline; the 5-Fu conventional dose group [5-Fu maximum tolerated dose (MTD) group], intraperitoneally injected with 50 mg/kg, twice per week for 2 weeks, with an 1-week discontinuation for 6 weeks; the capecitabine conventional dose group (capecitabine MTD group), intragastric 500 mg/kg, twice per week for 2 weeks, with a 1-week discontinuation for 6 weeks; the 5-Fu metronomic group [5-Fu low-dose metronomic (LDM) group], intraperitoneally injected with 15 mg/kg, twice a week for 6 weeks; and the capecitabine metronomic group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a week for 6 weeks...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344217/aleukemic-extramedullary-t-lymphoid-myeloid-bilineage-hematopoietic-and-lymphoid-malignancy-with-progression-to-bilineage-leukemia-at-relapse-a-case-report
#19
Mengyao Wu, Xiaoqiu Li, Feng Tang, Ping Zhu, Tianling Ding, Yan Yuan, Tong Chen
Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the hematopoietic and lymphoid malignancies. The majority of patients present with leukemic symptoms in which blasts are observed in the peripheral blood (PB) or bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been reported with extramedullary infiltration as the initial symptom. The origin of the neoplastic cells in T/My bilineage malignancy has been documented as the hematopoietic stem cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344192/tslp-promotes-angiogenesis-of-human-umbilical-vein-endothelial-cells-by-strengthening-the-crosstalk-between-cervical-cancer-cells-and-eosinophils
#20
Bing Zhang, Chun-Yan Wei, Kai-Kai Chang, Jia-Jun Yu, Wen-Jie Zhou, Hui-Li Yang, Jun Shao, Jin-Jin Yu, Ming-Qing Li, Feng Xie
Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E)...
December 2017: Oncology Letters
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