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Stephen E McGowan, Diann M McCoy
Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Zhen-Guo Ma, Xin Zhang, Yu-Pei Yuan, Ya-Ge Jin, Ning Li, Chun-Yan Kong, Peng Song, Qi-Zhu Tang
T cell infiltration and the subsequently increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure. A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cells-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro...
March 14, 2018: Clinical Science (1979-)
Federica Camela, Marcella Gallucci, Emanuela di Palmo, Salvatore Cazzato, Mario Lima, Giampaolo Ricci, Andrea Pession
The inflammatory myofibroblastic tumor (IMT) is a rare lesion of unclear etiology and variable clinical course, consisting of a proliferation of fibroblasts and myofibroblasts, mixed with inflammatory cells. Synonyms of IMT are inflammatory pseudotumor and plasma cell granuloma reflecting the alleged inflammatory nature attributed to this lesion, even though this heterogeneity in the disease denomination is probably involved in a dispersion of the literature data. Among primary pulmonary neoplasms, it represents the most frequent endobronchial tumor of childhood and beyond the lung it has been described mainly in the bladder, mediastinum and mesentery...
2018: Frontiers in Pediatrics
Jun Wei, Roberta G Marangoni, Feng Fang, Wenxia Wang, Jingang Huang, Joerg H W Distler, John Varga
The mechanisms underlying persistent fibroblast activation and myofibroblast phenoconversion in underlying multi-organ fibrosis in systemic sclerosis (SSc) remain incompletely understood, hindering effective therapies to slow or reverse the process. Cyclin-dependent kinase 5 (CDK5) is a pleiotropic member of the CDK family originally identified in neuronal cells. In contrast to other CDKs, CDK5 activity depends on its CDK5R1 subunit p35. Here we demonstrate that expression of p35 and CDK5 activity are induced by TGF-ß in fibroblasts and adipocytic cell types...
February 13, 2018: Oncotarget
Q Y Lao, M Sun, L Yu, J Wang
Objective: To investigate the clinicopathological characteristics and differential diagnosis of lipofibromatosis. Methods: The clinicopathological features and immunohistochemical profiles in 8 cases of lipofibromatosis diagnosed at Fudan University Shanghai Cancer Center from January 2008 to June 2017 were studied. Molecular analysis of β-catenin mutation by Sanger sequencing, NTKR1 and ETV6 rearrangements by FISH were performed. The follow up information was evaluated and the literature was reviewed. Results: There were 4 males and 4 females with a median age of 1...
March 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Paola Occhetta, Giuseppe Isu, Marta Lemme, Chiara Conficconi, Philipp Oertle, Christian Räz, Roberta Visone, Giulia Cerino, Marija Plodinec, Marco Rasponi, Anna Marsano
In vitro cardiac models able to mimic the fibrotic process are paramount to develop an effective anti-fibrosis therapy that can regulate fibroblast behaviour upon myocardial injury. In previously developed in vitro models, typical fibrosis features were induced by using scar-like stiffness substrates and/or potent morphogen supplementation in monolayer cultures. In our model, we aimed to mimic in vitro a fibrosis-like environment by applying cyclic stretching of cardiac fibroblasts embedded in three-dimensional fibrin-hydrogels alone...
March 13, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Gali Epstein Shochet, Lutz Wollin, David Shitrit
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. METHODS: IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM)...
March 12, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
Yangyang Gu, Bo Huang, Yanfei Yang, Mengdie Qi, Guohua Lu, Dajing Xia, Hequan Li
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung...
March 13, 2018: Inflammation
Vasundhara Kain, Kevin A Ingle, Janusz Kabarowski, Stephen Barnes, Nita A Limdi, Sumanth D Prabhu, Ganesh V Halade
12/15 lipoxygenase (LOX) directs inflammation and lipid remodeling. However, the role of 12/15LOX in post-myocardial infarction (MI) left ventricular remodeling is unclear. To determine the role of 12/15LOX, 8-12 week-old C57BL/6 J wild-type (WT; n = 93) and 12/15LOX-/- (n = 97) mice were subjected to permanent coronary artery ligation and monitored at day (d)1 and d5 post-operatively. Post-MI d28 survival was measured in male and female mice. No-MI surgery mice were maintained as d0 naïve controls...
March 8, 2018: Journal of Molecular and Cellular Cardiology
Fang Qiu, Changjiang Dong, Yanxin Liu, Xiaoqi Shao, Di Huang, Yanna Han, Bing Wang, Yanli Liu, Rong Huo, Petro Paulo, Zhiren Zhang, Dan Zhao, Wen-Feng Chu
BACKGROUND AND PURPOSE: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI). EXPERIMENTAL APPROACH: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function...
March 7, 2018: Toxicology and Applied Pharmacology
Sofia Ferreira-Gonzalez, Wei-Yu Lu, Alexander Raven, Benjamin Dwyer, Tak Yung Man, Eoghan O'Duibhir, Philip J Starkey Lewis, Lara Campana, Tim J Kendall, Thomas G Bird, Nuria Tarrats, Juan-Carlos Acosta, Luke Boulter, Stuart J Forbes
Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression to prevent undesired proliferation. However, under pathological circumstances, senescence can adversely affect organ function, viability and regeneration. We have developed a mouse model of biliary senescence, based on the conditional deletion of Mdm2 in bile ducts under the control of the Krt19 promoter, that exhibits features of biliary disease. Here we report that senescent cholangiocytes induce profound alterations in the cellular and signalling microenvironment, with recruitment of myofibroblasts and macrophages causing collagen deposition, TGFβ production and induction of senescence in surrounding cholangiocytes and hepatocytes...
March 9, 2018: Nature Communications
J S Lawson, H M Syme, C P D Wheeler-Jones, J Elliott
BACKGROUND: Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1...
March 9, 2018: BMC Veterinary Research
Tao Wang, Hao Zou, Yun-Xia Liu, Xiao-Wen Zhang
Background: Paclitaxel (PTX) could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film (N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]) and evaluated its safety and efficiency using in vivo and in vitro experiments. Methods: The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FT-IR) measurements...
March 20, 2018: Chinese Medical Journal
Katherine D Walton, Darcy Mishkind, Misty R Riddle, Clifford J Tabin, Deborah L Gumucio
Efficient absorption of nutrients by the intestine is essential for life. In mammals and birds, convolution of the intestinal surface into finger-like projections called villi is an important adaptation that ensures the massive surface area for nutrient contact that is required to meet metabolic demands. Each villus projection serves as a functional absorptive unit: it is covered by a simple columnar epithelium that is derived from endoderm and contains a mesodermally derived core with supporting vasculature, lacteals, enteric nerves, smooth muscle, fibroblasts, myofibroblasts, and immune cells...
March 7, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
Tae Hwan Park, Soon Won Chung, Seung Yong Song, Dae Hyun Lew, Tai Suk Roh, Dong Won Lee
Although there is ample evidence showing that radiation therapy increases the risk of complications of breast reconstruction, the efficacy of human acellular dermal matrix (CGCryoDerm®) in immediate tissue expander breast reconstruction in the setting of postmastectomy radiation therapy has not been fully elucidated. In this study, we report our institutional experience with pertinent refined surgical technique, and determine whether acellular dermal matrices have a protective effect in this increasingly prevalent clinical setting...
March 6, 2018: Journal of Materials Science. Materials in Medicine
Mickael Orgeur, Marvin Martens, Georgeta Leonte, Sonya Nassari, Marie-Ange Bonnin, Stefan T Börno, Bernd Timmermann, Jochen Hecht, Delphine Duprez, Sigmar Stricker
Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling revealed a set of common genes regulated by all five transcription factors, which we propose as connective tissue core expression set...
March 6, 2018: Development
Akira Sugiyama, Yuka Hirano, Muneyoshi Okada, Hideyuki Yamawaki
Myofibroblasts contribute to the healing of infarcted areas after myocardial infarction through proliferation, migration, and production of extracellular matrix (ECM). Expression of endostatin, a cleaved fragment of type XVIII collagen, increases in the heart tissue of an experimental myocardial infarction model. In the present study, we examined the effect of endostatin on the function of myofibroblasts derived from an infarcted area. The myocardial infarction model was created by ligating the left anterior descending artery in rats...
March 6, 2018: International Journal of Molecular Sciences
G E Melling, S E Flannery, S A Abidin, H Clemmens, P Prajapati, E E Hinsley, S Hunt, J W F Catto, R D Coletta, M Mellone, G J Thomas, E K Parkinson, S S Prime, I C Paterson, D J Buttle, D W Lambert
The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblast, CAF) supportive of tumour cell invasion and metastasis...
February 28, 2018: Carcinogenesis
Jennifer M Richards, Jennie A M R Kunitake, Heather B Hunt, Alexa N Wnorowski, Debra W Lin, Adele L Boskey, Eve Donnelly, Lara A Estroff, Jonathan T Butcher
Calcific aortic valve disease (CAVD) is an inexorably degenerative pathology characterized by progressive calcific lesion formation on the valve leaflets. The interaction of valvular cells in advanced lesion environments is not well understood yet highly relevant as clinically detectable CAVD exhibits calcifications composed of non-stoichiometric hydroxyapatite (HA). In this study, Fourier transform infrared spectroscopic imaging was used to spatially analyze mineral properties as a function of disease progression...
March 2, 2018: Acta Biomaterialia
Nicholas R Ladwig, J Kenneth Schoolmeester, Laura Weil, Jocelyn S Chapman, Charles Zaloudek, Sarah E Umetsu
Inflammatory myofibroblastic tumor (IMT) is a neoplasm of intermediate malignant potential that only rarely involves the gynecologic tract. Several cases of IMT arising in various locations including the lung, bladder, trachea, and breast in association with pregnancy have been reported in the literature, and 3 cases involving the placenta have been previously described. We report 2 cases of IMT identified in association with pregnancy; the first was an intrauterine mass delivered entirely separate from the placenta and fetus, and the second was an incidental mass identified within the placental parenchyma following delivery...
March 2, 2018: American Journal of Surgical Pathology
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