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https://www.readbyqxmd.com/read/29351444/activated-human-t-lymphocytes-inhibit-tgf%C3%AE-induced-fibroblast-to-myofibroblast-differentiation-via-prostaglandins-d2-and-e2
#1
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
#2
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
#3
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/29349703/matrix-stiffness-the-conductor-of-organ-fibrosis
#4
REVIEW
Alba Santos, David Lagares
PURPOSE OF REVIEW: Organ fibrosis is a lethal component of scleroderma. The hallmark of scleroderma fibrosis is extensive extracellular matrix (ECM) deposition by activated myofibroblasts, specialized hyper-contractile cells that promote ECM remodeling and matrix stiffening. The purpose of this review is to discuss novel mechanistic insight into myofibroblast activation in scleroderma. RECENT FINDINGS: Matrix stiffness, traditionally viewed as an end point of organ fibrosis, is now recognized as a critical regulator of tissue fibrogenesis that hijacks the normal physiologic wound-healing program to promote organ fibrosis...
January 19, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29349300/tensile-forces-drive-a-reversible-fibroblast-to-myofibroblast-transition-during-tissue-growth-in-engineered-clefts
#5
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
#6
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/29345973/r-spondin-2-is-upregulated-in-idiopathic-pulmonary-fibrosis-and-affects-fibroblasts-behavior
#7
Adrián Munguía-Reyes, Yalbi I Balderas-Martínez, Carina Becerril, Marco Checa, Remedios Ramírez, Blanca Ortíz-Quintero, Jorge Meléndez-Zajgla, Annie Pardo, Moisés Selman
Idiopathic pulmonary fibrosis (IPF) is characterized by the expansion of the myofibroblasts population, excessive extracellular matrix accumulation, and destruction of the lung parenchyma. The R-spondins family (RSPO) comprises a group of proteins essential for development. From them, RSPO2 is expressed primarily in the lungs and its mutations cause severe defects in the respiratory tract. Interestingly, RSPO2 participates in the canonical WNT pathway, a critical route in the pathogenesis of IPF. Thus, the aim of this study was to examine the expression and putative role of RSPO2 in this disease...
January 18, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29343655/spatiotemporal-alterations-of-autophagy-marker-lc3-in-rat-skin-fibroblasts-during-wound-healing-process
#8
Emiko Asai, Masaya Yamamoto, Kazuki Ueda, Satoshi Waguri
To investigate the possible implications of autophagy, one of the degradation pathways induced by metabolic stress, in the dynamic reconstructive process of wound healing, the appearance and changes of punctate structures for microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, were examined in a rat skin wound healing model. Although the ratio of LC3-II/LC3-I in Western blotting was not evidently changed during the wound healing process, LC3-positive dots were clearly observed in fibroblasts and myofibroblasts, and occasionally in macrophages, by immunohistofluorescence microscopy...
January 16, 2018: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/29340836/primary-culture-of-lung-fibroblasts-from-hyperoxia-exposed-rats-and-a-proliferative-characteristics-study
#9
Shi-Meng Zhao, Hong-Min Wu, Mei-Ling Cao, Dan Han
Lung fibrosis is an ultimate consequence of bronchopulmonary dysplasia (BPD) which shows the excessive proliferation of lung fibroblasts (LFs). To find a better model for studying the role of LFs in hyperoxia-induced lung fibrosis at the cellular level, we isolated LFs from the lung tissue of hyperoxia- and normoxia-exposed rat lungs on postnatal days 7, 14 and 21 for primary culture to study their proliferative behavior. In the present study, the LF predominance was > 95% in our culture method. The LFs isolated from rats exposed to hyperoxia in vivo showed significantly greater proliferation than that from normoxia-exposed rats...
January 16, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29339718/injury-activated-glial-cells-promote-wound-healing-of-the-adult-skin-in-mice
#10
Vadims Parfejevs, Julien Debbache, Olga Shakhova, Simon M Schaefer, Mareen Glausch, Michael Wegner, Ueli Suter, Una Riekstina, Sabine Werner, Lukas Sommer
Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29336663/lactobacillus-acidophilus-improves-intestinal-inflammation-in-an-acute-colitis-mouse-model-by-regulation-of-th17-and-treg-cell-balance-and-fibrosis-development
#11
Jin-Sil Park, JeongWon Choi, JooYeon Jhun, Ji Ye Kwon, Bo-In Lee, Chul Woo Yang, Sung-Hwan Park, Mi-La Cho
Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). Probiotics exert protective effects against IBD, and probiotic commensal Lactobacillus species are common inhabitants of the natural microbiota, especially in the gut. To investigate the effects of Lactobacillus acidophilus on the development of IBD, L. acidophilus was administered orally in mice with dextran sodium sulfate (DSS)-induced colitis...
January 16, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29336647/inflammatory-myofibroblastic-tumor-of-the-tongue-report-of-a-pediatric-case-and-review-of-the-literature
#12
Chiara Caporalini, Selene Moscardi, Angela Tamburini, Nicola Pierossi, Marco Di Maurizio, Anna Maria Buccoliero
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal lesion composed of myofibroblastic and fibroblastic spindle cells, accompanied by inflammatory infiltration. IMT may occur in the tongue. Five cases have been previously reported at this site. CASE REPORT: An inflammatory myofibroblastic tumor arose in the tongue of a 10 month old infant, confirmed by anaplastic lymphoma kinase (ALK) immunohistochemical staining and the clinical response to the tyrosine kinase inhibitor...
January 16, 2018: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/29330473/endothelial-heparan-sulfate-deficiency-reduces-inflammation-and-fibrosis-in-murine-diabetic-nephropathy
#13
Ditmer T Talsma, Kirankumar Katta, Marieke A B Ettema, Berna Kel, Marion Kusche-Gullberg, Moh R Daha, Coen A Stegeman, Jacob van den Born, Lianchun Wang
Inflammation plays a vital role in the development of diabetic nephropathy, but the underlying regulatory mechanisms are only partially understood. Our previous studies demonstrated that, during acute inflammation, endothelial heparan sulfate (HS) contributes to the adhesion and transendothelial migration of leukocytes into perivascular tissues by direct interaction with L-selectin and the presentation of bound chemokines. In the current study, we aimed to assess the role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic nephropathy mouse model...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29330036/regulation-of-fibrotic-changes-by-the-synergistic-effects-of-cytokines-dimensionality-and-matrix-towards-the-development-of-an-in-vitro-human-dermal-hypertrophic-scar-model
#14
Shikha Chawla, Sourabh Ghosh
Current therapeutic strategies to reduce scarring in full thickness skin defect offer limited success due to poor understanding of scar tissue formation and the underlying signaling pathways. There is an urgent need to develop human cell based in vitro scar tissue models as animal testing is associated with ethical and logistic complications and inter-species variations. Pro-inflammatory cytokines play critical role in regulating scar development through complex interplay and interaction with the ECM and corresponding signaling pathways...
January 9, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29328529/hinokitiol-ablates-myofibroblast-activation-in-precancerous-oral-submucous-fibrosis-by-targeting-snail
#15
Hui-Wen Yang, Ming-Yi Lu, Yu-Wei Chiu, Yi-Wen Liao, Yu-Feng Huang, Pin Ju Chueh, Pei-Ling Hsieh, Cheng-Chia Yu
Oral submucous fibrosis (OSF) is a precancerous condition with symptoms of limited mouth opening and areca nut chewing habit has been implicated in its pathogenesis. Hinokitiol, a natural tropolone derived from Chamacyparis taiwanensis, has been reported to improve oral lichen planus and inhibit various cancer cells. Here, we showed that hinokitiol reduced the myofibroblast activities in fBMFs and prevented the arecoline-induced transdifferentiation. Treatment of hinokitiol dose-dependently downregulated the myofibroblast markers as well as various EMT transcriptional factors...
January 12, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29325250/-myofibroma-myofibromatosis-a-clinicopathologic-analysis-of-9-cases
#16
Y Fu, W Y Guan, H Y Wu, H Y Wu, Z W Fan, Q Ye, F Q Meng
Objective: To investigate the clinical and histological features, diagnosis and differential diagnosis of myofibroma/myofibromatosis. Methods: The clinical data and pathology features of nine cases of myofibroma/myofibromatosis were collected from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing University Medical School and Children's Hospital of Nanjing Medical University. Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion were performed and relevant literature reviewed...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29322373/epac-is-required-for-exogenous-and-endogenous-stimulation-of-adenosine-a2b-receptor-for-inhibition-of-angiotensin-ii-induced-collagen-synthesis-and-myofibroblast-differentiation
#17
Sarawuth Phosri, Kwanchai Bunrukchai, Warisara Parichatikanond, Vilasinee H Sato, Supachoke Mangmool
Angiotensin II (Ang II) plays an important role on the pathogenesis of cardiac fibrosis. Prolong and overstimulation of angiotensin II type 1 receptor with Ang II-induced collagen synthesis and myofibroblast differentiation in cardiac fibroblasts, leading to cardiac fibrosis. Although adenosine and its analogues are known to have cardioprotective effects, the mechanistic by which adenosine A2 receptors (A2Rs) inhibit Ang II-induced cardiac fibrosis is not clearly understood. In the present study, we examined the effects of exogenous adenosine and endogenous adenosine on Ang II-induced collagen and myofibroblast differentiation determined by α-smooth muscle action (α-SMA) overexpression and their underlying signal transduction...
January 10, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29321510/a-model-of-human-lung-fibrogenesis-for-the-assessment-of-anti-fibrotic-strategies-in-idiopathic-pulmonary-fibrosis
#18
Katy M Roach, Amanda Sutcliffe, Laura Matthews, Gill Elliott, Chris Newby, Yassine Amrani, Peter Bradding
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. KCa3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective KCa3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320561/%C3%AE-smooth-muscle-actin-is-not-a-marker-of-fibrogenic-cell-activity-in-skeletal-muscle-fibrosis
#19
Wanming Zhao, Xingyu Wang, Kai-Hui Sun, Lan Zhou
α-Smooth muscle actin (α-SMA) is used as a marker for a subset of activated fibrogenic cells, myofibroblasts, which are regarded as important effector cells of tissue fibrogenesis. We address whether α-SMA-expressing myofibroblasts are detectable in fibrotic muscles of mdx5cv mice, a mouse model for Duchenne muscular dystrophy (DMD), and whether the α-SMA expression correlates with the fibrogenic function of intramuscular fibrogenic cells. α-SMA immunostaining signal was not detected in collagen I (GFP)-expressing cells in fibrotic muscles of ColI-GFP/mdx5cv mice, but it was readily detected in smooth muscle cells lining intramuscular blood vessel walls...
2018: PloS One
https://www.readbyqxmd.com/read/29315443/pathophysiology-of-corneal-scarring-in-persistent-epithelial-defects-after-prk-and-other-corneal-injuries
#20
Steven E Wilson, Carla S Medeiros, Marcony R Santhiago
PURPOSE: To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. METHODS: Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK...
January 1, 2018: Journal of Refractive Surgery
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