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Fibrogenesis

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https://www.readbyqxmd.com/read/28935574/taurocholate-induces-biliary-differentiation-of-liver-progenitor-cells-causing-hepatic-stellate-cell-chemotaxis-in-the-ductular-reaction-role-in-pediatric-cystic-fibrosis-liver-disease
#1
Katarzyna N Pozniak, Michael A Pearen, Tamara N Pereira, Cynthia Sm Kramer, Priyakshi Kalita-De Croft, Sujeevi K Nawaratna, Manuel A Fernandez-Rojo, Geoffrey N Gobert, Janina Ee Tirnitz-Parker, John K Olynyk, Ross W Shepherd, Peter J Lewindon, Grant A Ramm
Cystic fibrosis liver disease (CFLD) in children causes progressive fibrosis leading to biliary cirrhosis, however its cause(s) and early pathogenesis are unclear. We hypothesised that a bile acid-induced Ductular Reaction (DR) drives fibrogenesis. We evaluated the DR by cytokeratin-7 immunohistochemistry in liver biopsies, staged for fibrosis, from 60 children with CFLD and demonstrated that the DR was significantly correlated with hepatic fibrosis stage and biliary taurocholate levels. To examine the mechanisms involved in DR induction liver progenitor cells (LPCs) were treated with taurocholate and key events in DR evolution were assessed: LPC proliferation, LPC biliary differentiation and hepatic stellate cell (HSC) chemotaxis...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28934669/transforming-growth-factor-beta-tgf-%C3%AE-mediates-cardiac-fibrosis-and-induces-diabetic-cardiomyopathy
#2
REVIEW
Yiyang Yue, Ke Meng, Yuejie Pu, Xiaoming Zhang
Cardiovascular diseases account for the major cause of morbidity and mortality among individuals with diabetes. The diabetic cardiomyopathy (DCM) is a type of diabetic cardiovascular disease, which further directs to the heart failure. The researchers found that diabetes induced cardiac fibrosis plays a vital role in several of the pathological changes that associated with DCM, causing left ventricular hypertrophy (LVH), diastolic dysfunction and systolic dysfunction. However, the mechanisms involved in the pathogenesis of DCM are still elusive...
September 1, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28933600/a-novel-acetyltransferase-p300-inhibitor-ameliorates-hypertension-associated-cardio-renal-fibrosis
#3
Rahul Rai, Suresh K Verma, David Kim, Veronica Ramirez, Elizabeth Lux, Chengjin Li, Susmita Sahoo, Lisa D Wilsbacher, Douglas E Vaughan, Susan E Quaggin, Asish K Ghosh
Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300-p300 with intrinsic factor acetyltransferase activity-is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28927974/infiltration-of-polarized-macrophages-associated-with-liver-fibrosis-in-infants-with-biliary-atresia
#4
Yifan Yang, Rui Dong, Chao Zheng, Shan Zheng, Gong Chen
BACKGROUND/PURPOSE: Macrophages exert critical functions in liver homeostasis and have been proposed as potential targets in combatting fibrosis. We aimed to evaluate polarized functional status of liver infiltrated macrophages in infants with biliary atresia (BA). METHODS: Immunohistochemical staining for CD68, CD163, and IRF5 was performed in 40 BA infants. Liver biopsies were scored for fibrosis and tested for association with clinical biochemical characteristics...
September 2, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#5
Debra F Higgins, Leah Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28919365/hepatic-stellate-cell-specific-deletion-of-sirt1-exacerbates-liver-fibrosis-in-mice
#6
Min Li, Wenxuan Hong, Chenzhi Hao, Luyang Li, Huihui Xu, Ping Li, Yong Xu
Liver fibrosis is widely perceived as a host defense mechanism that aids tissue repair following liver injury. Excessive fibrogenesis, however, serves to disrupts normal liver structure and precedes such irrevocable human pathologies as cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrosis. In the present study we investigated the mechanism by which the lysine deacetylase SIRT1 regulates HSC activation. We report here that SIRT1 levels were decreased in the liver in different mouse models and in cultured HSCs undergoing activation...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#7
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#8
Seidai Sato, Shintaro Shinohara, Shinya Hayashi, Shun Morizumi, Shuichi Abe, Hiroyasu Okazaki, Yanjuan Chen, Hisatsugu Goto, Yoshinori Aono, Hirohisa Ogawa, Kazuya Koyama, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka
BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear...
September 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28902427/nlrp3-inflammasome-driven-liver-injury-and-fibrosis-roles-of-il-17-and-tnf
#9
Alexander Wree, Matthew D McGeough, Maria Eugenia Inzaugarat, Akiko Eguchi, Susanne Schuster, Casey D Johnson, Carla A Peña, Lukas J Geisler, Bettina G Papouchado, Hal M Hoffman, Ariel E Feldstein
The NLRP3 inflammasome, a caspase-1 activation platform plays a key role in the modulation of liver inflammation and fibrosis. Here, we tested the hypothesis that interleukin 17 (IL-17) and tumor necrosis factor (TNF) are key cytokines involved in amplifying and perpetuating the liver damage and fibrosis resulting from NLRP3 activation. To address this hypothesis gain of function Nlrp3(A350V) knock-in mice were bred onto il17a and Tnf knockout backgrounds allowing for constitutive Nlrp3 activation in myeloid derived cells in mice deficient in IL-17 or TNF...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28901271/the-role-of-cannabinoid-receptors-in-renal-diseases
#10
Hélène François, Lola Lecru
Chronic kidney disease (CKD) remains a major challenge for Public Health systems and corresponds to the replacement of renal functional tissue by extra-cellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for CKD except nephroprotective strategies. The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in CKD. Our review will first focus on the current state of knowledge regarding the cannabinoid system in normal renal physiology and in various experimental nephropathies, especially diabetes...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28899682/caveolin-1-controls-hyperresponsiveness-to-mechanical-stimuli-and-fibrogenesis-associated-runx2-activation-in-keloid-fibroblasts
#11
Chao-Kai Hsu, Hsi-Hui Lin, Hans I-Chen Harn, Rei Ogawa, Yang-Kao Wang, Yen-Ting Ho, Wan-Rung Chen, Yi-Chao Lee, Julia Yu-Yun Lee, Shyh-Jou Shieh, Chao-Min Cheng, John A McGrath, Ming-Jer Tang
Keloids are pathological scars characterized by excessive extracellular matrix production that are prone to form in body sites with increased skin tension. Caveolin-1 (CAV1), the principal coat protein of caveolae, has been associated with the regulation of cell mechanics, including cell softening and loss of stiffness sensing ability in NIH3T3 fibroblasts. Although CAV1 is present in low amounts in keloid fibroblasts (KFs), the causal association between CAV1 downregulation and its aberrant responses to mechanical stimuli remain unclear...
September 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28895372/-tipping-extracellular-matrix-remodelling-towards-regression-of-liver-fibrosis-novel-concepts
#12
Fernando Magdaleno, Robert Schierwagen, Frank E Uschner, Jonel Trebicka
Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, as well as other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC)...
September 11, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28894272/t-cell-tolerance-and-exhaustion-in-the-clearance-of-echinococcus-multilocularis-role-of-inoculum-size-in-a-quantitative-hepatic-experimental-model
#13
Chuanshan Zhang, Yingmei Shao, Shuting Yang, Xiaojuan Bi, Liang Li, Hui Wang, Ning Yang, Zhide Li, Cheng Sun, Liang Li, Guodong Lü, Tuerganaili Aji, Dominique A Vuitton, Renyong Lin, Hao Wen
The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development of E. multilocularis larvae. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose-infected mice (LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice (HDG)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890699/sphingosine-1-phosphate-signaling-as-a-target-in-hepatic-fibrosis-therapy
#14
REVIEW
Bárbara González-Fernández, Diana I Sánchez, Javier González-Gallego, María J Tuñón
Liver fibrosis is an excess production of extracellular matrix proteins as a result of chronic liver disease which leads to cell death and organ dysfunction. The key cells involved in fibrogenesis are resident hepatic stellate cells (HSCs) which are termed myofibroblasts after activation, acquiring contractile, proliferative, migratory and secretory capability. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and immunity. Accumulating evidence demonstrates that this metabolite is involved in the profibrotic inflammatory process through the regulation of pleiotropic cell responses, such as vascular permeability, leukocyte infiltration, cell survival, migration, proliferation and HSCs differentiation to myofibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28889072/the-haemocytes-of-the-colonial-aplousobranch-ascidian-diplosoma-listerianum-structural-cytochemical-and-functional-analyses
#15
Francesca Cima, Anna Peronato, Loriano Ballarin
Diplosoma listerianum is a colonial aplousobranch ascidian of the family Didemnidae that is native to the northeast Atlantic and exhibits a cosmopolitan distribution in temperate waters. It lacks a shared colonial circulation crossing the tunic, and the zooids are connected only by the common tunic. In the present study, the haemocytes of this ascidian were analysed via light and electron microscopy. Their phagocytic and enzymatic activities, staining and immunostaining properties, and lectin affinity were examined with various classical methods reconsidered and modified for small marine invertebrates...
August 30, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28884741/-the-nephroprotective-potential-of-peloid-therapy-used-for-the-rehabilitation-of-the-patients-presenting-with-chronic-pyelonephritis
#16
E I Slobodian, N N Kaladze, A L Govdaliuk, E I Kulik
This review article presents the data on the mechanism of action of peloid therapy from the perspective of its defibrosing effect, the structure and functions of the extracellular matrix under the normal and pathological conditions. In addition, role of this treatment modality in the progression of tubulointerstitial fibrosis which determines the severity and prognosis of chronic pyelonephritis is considered. The researchers are currently carry out the extensive studies aimed at the search of the methods for the primary and secondary prevention of chronic pyelonephritis...
2017: Voprosy Kurortologii, Fizioterapii, i Lechebnoĭ Fizicheskoĭ Kultury
https://www.readbyqxmd.com/read/28880053/liver-fibrosis-the-2017-state-of-art
#17
Gian P Caviglia, Chiara Rosso, Sharmila Fagoonee, Giorgio M Saracco, Rinaldo Pellicano
Liver fibrosis is a wound-healing response to a wide spectrum of chronic liver injuries. It is characterized by loss of hepatocytes and alteration in hepatic architecture following an imbalance between extracellular matrix synthesis and degradation. Irrespectively of underlying etiology, fibrosis may progress to cirrhosis and specific pathogenetic mechanisms as well as different disease patterns may be identified according to etiology. Liver biopsy is still considered the gold standard for fibrosis assessment, despite the fact that it is invasive, has poor patient compliance and is not exempt of complications...
September 5, 2017: Panminerva Medica
https://www.readbyqxmd.com/read/28877670/indoleamine-2-3-dioxygenase-ido-increases-during-renal-fibrogenesis-and-its-inhibition-potentiates-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition
#18
Luiz Henrique Gomes Matheus, Gislene Mendes Simão, Taíssa Altieri Amaral, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Yves Silva Teles Matos, Alexandre Chagas Santana, Gabriela Gomes Cardoso Rodrigues, Maria Clara Albejante, Erna Elisabeth Bach, Maria Aparecida Dalboni, Cleber Pinto Camacho, Humberto Dellê
BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is an immunomodulatory molecule that has been implicated in several biological processes. Although IDO has been linked with some renal diseases, its role in renal fibrosis is still unclear. Because IDO may be modulated by TGF-β1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-β1-induced tubular epithelial-mesenchymal transition (EMT). We analyzed the IDO expression and activity in a model of renal fibrogenesis, and the effect of the IDO inhibitor 1-methyl-tryptophan (MT) on TGF-β1-induced EMT using tubular cell culture...
September 6, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28875689/liver-fibrosis-in-the-context-of-nonalcoholic-steatohepatitis-the-role-of-adipokines
#19
Giovanni DI Maira, Mirella Pastore, Fabio Marra
Liver fibrosis is a multifaceted process that occurs as a consequence of chronic liver injury. This process is characterized by inflammation, activation of matrix-producing cells, matrix deposition and remodeling, and epithelial cell regeneration. In subjects with chronic liver damage, fibrogenesis is favored by the presence of obesity and insulin resistance, which are also relevant risk factors for the development and progression of nonalcoholic steatohepatitis (NASH). It is now well-known that adipose tissue is not only involved in energy storage but also functions as an endocrine organ that secretes various bioactive substances known as adipokines...
September 5, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28871223/effects-of-enzymatically-depolymerized-low-molecular-weight-heparins-on-ccl4-induced-liver-fibrosis
#20
Yishu Yan, Changge Guan, Shanshan Du, Wenming Zhu, Yang Ji, Nan Su, Xiang Mei, Dong He, Yuan Lu, Chong Zhang, Xin-Hui Xing
With regard to identifying the effective components of LMWH drugs curing hepatic fibrosis disease, we carried out a comparative study on the efficacy of enzymatically depolymerized LMWHs on CCl4 induced mouse liver fibrosis. The results showed that the controlled enzymatic depolymerization conditions resulted in LMWHs with significantly different activities. The LMWH product depolymerized by Heparinase I (I-11) with a Mw of 7160, exhibited a significant advantage in reducing the liver inflammation by suppressing TNF-α and IL-1β secretion, and minimizing hepatic fibrogenesis...
2017: Frontiers in Pharmacology
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