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Takafumi Kawamura, Masayoshi Yamamoto, Katsunori Suzuki, Yuhi Suzuki, Megumu Kamishima, Mayu Sakata, Kiyotaka Kurachi, Mitsutoshi Setoh, Hiroyuki Konno, Hiroya Takeuchi
Background: Colitis-associated cancer (CAC) is one of the prognostic factors in inflammatory bowel disease (IBD), and prevention of CAC is a critical concern for patients with IBD. Component cells of the microenvironment, especially myofibroblasts, are known to affect tumor development, but the role of intestinal myofibroblasts (IMFs) in CAC has not been clarified. Here, we explored the role of IMFs in CAC and sought to identify candidate genes as novel therapeutic targets for the prevention of CAC...
December 4, 2018: Inflammatory Bowel Diseases
Chang Yung Chia, Andréia Dantas Medeiros, André de Menezes Silva Corraes, José Eduardo Ferreira Manso, César Silveira Claudio da Silva, Christina Maeda Takiya, Ricardo Luís Vanz
PURPOSE: To evaluate the effects and mechanisms of andiroba-based emulsion (ABE) topical treatment on full-thickness cutaneous wounds in rats. METHODS: The wounds were harvested on days 3, 7, 15, and 20 post-surgery. Wound contraction rate, quantitative immunohistochemistry [macrophages, myofibroblasts, capillaries, collagens (col) I and III, transforming growth factor β3β (TGFβ3)], and tensile strength were assessed. RESULTS: Treated wounds were smaller, contracted earlier and had increased angiogenesis, fewer CD68+ and M2 macrophages on days 7 and 15, but higher on day 20...
November 2018: Acta Cirúrgica Brasileira
Miao Zhang, Meng-Zhou Zhang, Shu-Heng Wen, Ying-Fu Sun, Peng-Hao Jiang, Lin-Lin Wang, Rui Zhao, Chang-Liang Wang, Shu-Kun Jiang, Da-Wei Guan
HIPK2 is an evolutionarily conserved serine/threonine kinase and is considered a co-regulator of an increasing number of transcription factors modulating a variety of cellular processes, including inflammation, proliferation and fibrosis. Skeletal muscle injuries repair is an overlapping event between inflammation and tissue repair. There are no reports about HIPK2 expression in skeletal muscles after trauma. A foundational study on distribution and time-dependent expression of HIPK2 was performed by immunohistochemical staining, Western blotting and quantitative real-time PCR, which is expected to obtain a preliminary insight into the functions of HIPK2 during the repair of contused skeletal muscle in mice...
December 5, 2018: Histology and Histopathology
Amy Inji Chang, Young Kon Kim, Ji Hye Min, Jisun Lee, Honsoul Kim, Soon Jin Lee
PURPOSE: To determine the differential features of inflammatory myofibroblastic tumor (IMT) and intrahepatic cholangiocarcinoma (ICC) manifesting as target appearance on gadoxetic acid-enhanced MRI. METHODS: Twenty-seven patients with 36 IMTs (1.2-6.0 cm) and 34 patients with 34 ICCs (1.5-6.0 cm) who underwent gadoxetic acid-enhanced MRI were enrolled in this study. Two reviewers evaluated morphology, signal intensity, and enhancement features of tumors on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and gadoxetic acid-enhanced imaging...
December 4, 2018: Abdominal Radiology
Chung-Jung Liu, Yao-Kuang Wang, Fu-Chen Kuo, Wen-Hung Hsu, Fang-Jung Yu, Shuchen Hsieh, Ming-Hong Tai, Deng-Chyang Wu, Chao-Hung Kuo
Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori ( H. pylori ) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer...
November 30, 2018: Cancers
Ming-Dan Deng, Jun-Yang Han, Ke Lin, Hong Tang
RATIONALE: Cardiac inflammatory myofibroblastic tumor (IMT) is a rare primary cardiac tumor which is currently considered as a low-grade neoplasm. The tumor has a predilection in infants and adolescents and primarily occurs as an endocardial-based cavitary mass. However, cardiac IMT that only involves the interventricular septum in middle-aged adults is extremely rarely reported. Considering its infrequency, we report a rare clinical case, with the aim of sharing our experience during the diagnostic procedures...
November 2018: Medicine (Baltimore)
Marie Fukutake, Daigo Ochiai, Hirotaka Masuda, Yushi Abe, Yu Sato, Toshimitsu Otani, Shigeki Sakai, Noriko Aramaki-Hattori, Masayuki Shimoda, Tadashi Matsumoto, Kei Miyakoshi, Yae Kanai, Kazuo Kishi, Mamoru Tanaka
Adult wound healing can result in fibrotic scarring (FS) characterized by excess expression of myofibroblasts and increased type I/type III collagen expression. In contrast, fetal wound healing results in complete regeneration without FS, and the mechanism remains unclear. Amniotic fluid cells could contribute to scar-free wound healing, but the effects of human amniotic fluid cells are not well characterized. Here, we determined the effect of human amniotic fluid stem cells (hAFS) on FS during wound healing...
December 1, 2018: Human Cell
Emma K Libby, Lindsey T Ellis, Stephen Weinstein, Richard D Hammer, Katie S Murray
A 61-year-old male presented with gross hematuria and transurethral resection of bladder tumor revealed inflammatory myofibroblastic tumor (IMT). Due to extent of disease leading to ureteral obstruction and hydronephrosis, radical cystectomy (RC) with ileal conduit urinary diversion was performed. Five months after RC, the patient presented with decreased urine output. Exploratory laparotomy revealed mass in right colon and right hemicolectomy revealed metastatic IMT to the bowel and pericolonic fat. To our knowledge, this is the first report of primary IMT of the bladder metastasizing to other organs...
March 2019: Urology Case Reports
Andreia V Pinho, Mathias Van Bulck, Lorraine Chantrill, Mehreen Arshi, Tatyana Sklyarova, David Herrmann, Claire Vennin, David Gallego-Ortega, Amanda Mawson, Marc Giry-Laterriere, Astrid Magenau, Gunther Leuckx, Luc Baeyens, Anthony J Gill, Phoebe Phillips, Paul Timpson, Andrew V Biankin, Jianmin Wu, Ilse Rooman
Whereas genomic aberrations in the SLIT-ROBO pathway are frequent in pancreatic ductal adenocarcinoma (PDAC), their function in the pancreas is unclear. Here we report that in pancreatitis and PDAC mouse models, epithelial Robo2 expression is lost while Robo1 expression becomes most prominent in the stroma. Cell cultures of mice with loss of epithelial Robo2 (Pdx1Cre ;Robo2F/F ) show increased activation of Robo1+ myofibroblasts and induction of TGF-β and Wnt pathways. During pancreatitis, Pdx1Cre ;Robo2F/F mice present enhanced myofibroblast activation, collagen crosslinking, T-cell infiltration and tumorigenic immune markers...
November 30, 2018: Nature Communications
Signe Holm Nielsen, Nicholas Willumsen, Diana Julie Leeming, Samuel Joseph Daniels, Susanne Brix, Morten Asser Karsdal, Federica Genovese, Mette Juul Nielsen
OBJECTIVES: Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which has been found to be upregulated in lung fibrosis and cancer. We evaluated the potential of α-SMA as a noninvasive biomarker of activated fibroblasts in lung fibrosis and cancer. METHODS: A monoclonal antibody was raised against the N-terminal of α-SMA, and a novel competitive enzyme-linked immunosorbent assay (ELISA) measuring α-SMA was developed and technically characterized...
November 29, 2018: Translational Oncology
Faik Imeri, Karen A Nolan, Andreas M Bapst, Sara Santambrogio, Irene Abreu-Rodríguez, Patrick Spielmann, Svende Pfundstein, Silvana Libertini, Lisa Crowther, Ilaria M C Orlando, Sophie L Dahl, Anna Keodara, Willy Kuo, Vartan Kurtcuoglu, Carsten C Scholz, Weihong Qi, Edith Hummler, David Hoogewijs, Roland H Wenger
Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells...
November 23, 2018: Kidney International
Steven Mullenbrock, Fei Liu, Suzanne Szak, Xiaoping Hronowski, Benbo Gao, Peter Juhasz, Chao Sun, Mei Liu, Helen McLaughlin, Qiurong Xiao, Carol Feghali-Bostwick, Timothy S Zheng
Fibroblasts/myofibroblasts are the key effector cells responsible for excessive extracellular matrix (ECM) deposition and fibrosis progression in both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) patient lungs, thus it is critical to understand the transcriptomic and proteomic programs underlying their fibrogenic activity. We conducted the first integrative analysis of the fibrotic programming in these cells at the levels of gene and microRNA (miRNA) expression, as well as deposited ECM protein to gain insights into how fibrotic transcriptional programs culminate in aberrant ECM protein production/deposition...
November 29, 2018: Genes
Liping Wang, Yinshen Yang, Xiaoqin Xiong, Ting Yu, Xinhong Wang, Wenxia Meng, Haiyan Wang, Gang Luo, Linhu Ge
BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease in which comprehensive inflammation-related cytokines are involved. These cytokines are commonly produced by immune cells and specific nonimmune cells including keratinocytes, endothelial cells and fibroblasts. This raises the question of whether fibroblasts in OLP lesions contribute to the inflammatory process upon inflammatory simulation. METHODS: Primary cultured Oral lichen-planus-associated fibroblasts (OLP AFs, n = 5) and normal buccal mucosal fibroblasts (NFs, n = 5) were examined by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reactions (RT-PCR)...
November 29, 2018: BMC Oral Health
Michaela Bártů, Pavel Dundr, Kristýna Němejcová, Petra Prokopová, Iva Zambo, Štěpán Černý
Here we report on the case of a 61-year-old female with an accidental finding of intravascular fasciitis (IVF) affecting the ascending aorta in a specimen resected due to an acute aortic dissection. No infiltrative process of the aorta or surrounding soft tissues was grossly apparent. Microscopically, the lesion had poorly defined margins and was composed of plump spindle- and oval-shaped cells set in an abundant myxoid stroma. Immunohistochemically, cytoplasmic positivity for β-catenin was observed and about 25% of cells were positive for calponin...
2018: Ceskoslovenská Patologie
Natalie Landry, Morvarid S Kavosh, Krista L Filomeno, Sunil G Rattan, Michael P Czubryt, Ian M C Dixon
Many etiologies of heart disease are characterized by expansion and remodeling of the cardiac extracellular matrix (ECM or matrix) which results in cardiac fibrosis. Cardiac fibrosis is mediated in cardiac fibroblasts by TGF-β1 /R-Smad2/3 signaling. Matrix component proteins are synthesized by activated resident cardiac fibroblasts known as myofibroblasts (MFB). These events are causal to heart failure with diastolic dysfunction and reduced cardiac filling. We have shown that exogenous Ski, a TGF-β1 /Smad repressor, localizes in the cellular nucleus and deactivates cardiac myofibroblasts...
November 2018: Physiological Reports
Jin Wu, Xuran Chu, Chengshui Chen, Saverio Bellusci
During organogenesis and pathogenesis, fibroblast growth factor 10 (Fgf10) regulates mesenchymal cell differentiation in the lung. Different cell types reside in the developing lung mesenchyme. Lineage tracing in vivo was used to characterize these cells during development and disease. Fgf10-positive cells in the early lung mesenchyme differentiate into multiple lineages including smooth muscle cells (SMCs), lipofibroblasts (LIFs) as well as other cells, which still remain to be characterized. Fgf10 signaling has been reported to act both in an autocrine and paracrine fashion...
2018: Frontiers in Genetics
Patrick Sieber, Anny Schäfer, Raphael Lieberherr, François Le Goff, Manuel Stritt, Richard W D Welford, John Gatfield, Oliver Peter, Oliver Nayler, Urs Lüthi
Pathological features of pulmonary fibrosis include accumulation of myofibroblasts and increased extracellular matrix (ECM) deposition in lung tissue. Contractile α-smooth muscle actin (α-SMA)-expressing myofibroblasts that produce and secrete ECM are key effector cells of the disease and therefore represent a viable target for potential novel anti-fibrotic treatments. We used primary normal human lung fibroblasts (NHLF) in two novel high-throughput screening assays to discover molecules that inhibit or revert fibroblast-to-myofibroblast differentiation...
2018: PloS One
Bo Jin, Jun Zhu, Hai-Ming Shi, Zhi-Chao Wen, Bang-Wei Wu
Yes-associated protein (YAP) is an important regulator of cellular proliferation and transdifferentiation. However, little is known about the mechanisms underlying myofibroblast transdifferentiation in dilated cardiomyopathy (DCM). We investigated the role of YAP in the pathological process of cardiac matrix remodeling. A classic model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Cardiac fibroblasts were isolated from neonatal Sprague-Dawley rats by density gradient centrifugation...
November 23, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Jiamin Wen, Xianchai Lin, Wuyou Gao, Bo Qu, Yunlan Ling, Rongjiao Liu, Minbin Yu
Subconjunctival fibrosis represents the primary cause of postoperative failure of trabeculectomy, and at present there is a lack of effective intervention strategies. The present study aimed to investigate the effect of the mitogen‑activated protein kinase kinase (MEK) inhibitor U0126 on human tenon fibroblast (HTF) myofibrosis transdifferentiation, and to illuminate the underlying molecular mechanisms involved. It was demonstrated that U0126 significantly inhibited the proliferation, migration and collagen contraction of HTFs stimulated with TGF‑β1...
November 20, 2018: Molecular Medicine Reports
Wei Hou, Wing-Kin Syn
Activation of hepatic stellate cell (HSC) involves the transition from a quiescent to a proliferative, migratory, and fibrogenic phenotype (i.e., myofibroblast), which is characteristic of liver fibrogenesis. Multiple cellular and molecular signals which contribute to HSC activation have been identified. This review specially focuses on the metabolic changes which impact on HSC activation and fibrogenesis.
2018: Frontiers in Cell and Developmental Biology
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