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Fibrogenesis

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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/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#2
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29349703/matrix-stiffness-the-conductor-of-organ-fibrosis
#3
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/29348414/microrna-146a-5p-attenuates-irradiation-induced-and-lps-induced-hepatic-stellate-cell-activation-and-hepatocyte-apoptosis-through-inhibition-of-tlr4-pathway
#4
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29336497/effects-of-treatment-with-maraviroc-a-ccr5-inhibitor-on-a-human-hepatic-stellate-cell-line
#5
N Coppola, A Perna, A Lucariello, S Martini, M Macera, M A Carleo, G Guerra, V Esposito, A De Luca
After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated following several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis...
January 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29329377/endometrial-stem-cell-derived-g-csf-attenuates-endometrial-fibrosis-via-sonic-hedgehog-transcriptional-activator-gli2
#6
Xiaona Lin, Yanling Zhang, Yibin Pan, Shilin He, Yongdong Dai, Bingqing Zhu, Cheng Wei, Liaobing Xin, Wenzhi Xu, Chunsheng Xiang, Songying Zhang
Intrauterine adhesion (IUA) is characterized by endometrial fibrosis, which ultimately leads to menstrual abnormalities, infertility and recurrent miscarriages. The Shh/Gli2 pathway plays a critical role in tissue fibrogenesis and regeneration; Gli2 activation induces profibrogenic effects in various tissues, such as the liver and kidney. However, the role of Gli2 in endometrial fibrosis remains unknown. The purpose of this study was to test the hypothesis that activated Gli2 promotes endometrial fibrosis. Endometrial samples from moderate and severe IUA patients exhibited significantly enhanced expression of Gli2 compared with normal endometrial samples and mild IUA samples...
January 10, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29325696/urinary-mrna-analysis-of-biomarkers-to-epithelial-mesenchymal-transition-of-renal-allograft
#7
Imen Mezni, Pierre Galichon, Mohammed Mongi Bacha, Yi-Chun Xu-Dubois, Imen Sfar, David Buob, Sabrina Benbouzid, Rim Goucha, Yousr Gorgi, Ezzedine Abderrahim, Mondher Ounissi, Karine Dahan, Nacera Ouali, Alexandre Hertig, Isabelle Brocheriou, Aly Raies, Taieb Ben Abdallah, Éric Rondeau
Renal allograft loss is most often a chronic process, irrespective of the mechanism at stake. In this prospective study, we studied the expression of epithelial to mesenchymal transition (EMT) markers vimentin and β-catenin by immunohistochemistry in the surveillance biopsy and measured the mRNA encoding vimentin (VIM), CD45, GAPDH and uroplakin 1a (UPK) by quantitative PCR in urinary cells in 75 renal transplant patients. The aim is to establish a simple screening test for chronic renal allograft dysfunction...
January 8, 2018: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29321510/a-model-of-human-lung-fibrogenesis-for-the-assessment-of-anti-fibrotic-strategies-in-idiopathic-pulmonary-fibrosis
#8
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
#9
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/29312604/serum-amyloid-a-induces-m2b-like-macrophage-polarization-during-liver-inflammation
#10
Yibin Wang, Haijun Huang, Renhua Sun, Bingyu Chen, Fang Han, Qian Li, Yin Ni, Xi Li, Jingquan Liu, Xiaozhou Mou, Yuexing Tu
Hepatitis causes hepatic cell injury, regeneration and different levels of fibrogenesis, and severe liver fibrogenesis progresses into cirrhosis with liver dysfunction. Serum amyloid A (SAA) is an acute phase protein that is predominantly secreted by hepatocytes during early injury or infection. Nevertheless, the relationship of SAA and development of cirrhosis as well as the underlying molecular mechanisms is largely unknown. Here, we found that macrophages are the major SAA-binding cells in the injured liver...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305935/hedgehog-yap-signaling-pathway-regulates-glutaminolysis-to-control-hepatic-stellate-cell-activation
#11
Kuo Du, Jeongeun Hyun, Richard T Premont, Steve S Choi, Gregory A Michelotti, Marzena Swiderska-Syn, George D Dalton, Eric Thelen, Bahar Salimian Rizi, Youngmi Jung, Anna Mae Diehl
BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes-associated protein 1 (YAP1 or YAP) and inducing aerobic glycolysis. However, increased aerobic glycolysis alone cannot meet the high metabolic demands of myofibroblastic HSCs. Determining the metabolic processes of these cells could lead to strategies to prevent progressive liver fibrosis, so we investigated whether glutaminolysis (conversion of glutamine to alpha-ketoglutarate) sustains energy metabolism and permits anabolism when Q-HSCs become myofibroblastic, and whether this is controlled by hedgehog signaling to YAP...
January 3, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29296869/circulating-fibrocytes-as-biomarkers-of-impaired-lung-function-in-adults-with-sickle-cell-disease
#12
Borna Mehrad, Marie D Burdick, Nancy J Wandersee, Kaushik S Shahir, Liyun Zhang, Pippa M Simpson, Robert M Strieter, Joshua J Field
Lung injury and fibrosis are common in patients with sickle cell disease (SCD). Fibrocytes, a population of circulating, bone marrow-derived cells, have been linked to development and progression of tissue fibrogenesis and have been implicated in the development of lung fibrosis in preclinical models of SCD. We tested the hypothesis that the levels and activation state of circulating fibrocytes during steady state are associated with abnormal pulmonary function in adults with SCD. In a prospective cohort of steady-state adults with SCD and healthy age- and race-matched control participants, we measured the concentration and activation state of circulating fibrocytes and assessed pulmonary phenotype with pulmonary function tests (PFTs), a respiratory questionnaire, 6-minute walk test, high-resolution chest computed tomography scan, and echocardiogram...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289644/matrix-metalloproteinases-and-liver-fibrosis-translational-aspects
#13
REVIEW
Elke Roeb
Liver fibrosis, a reversible wound-healing response to chronic cellular injury, reflects a balance between liver repair and progressive substitution of the liver parenchyma by scar tissue. Complex mechanisms that underlie liver fibrogenesis are summarized to provide the basis for generating targeted therapies to reverse fibrogenesis and improve the outcomes of patients with chronic liver disease. This minireview presents some pathophysiological aspects of liver fibrosis as a dynamic process and elucidates matrix metalloproteinases (MMPs) and their role within as well as beyond matrix degradation...
December 28, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29287776/activin-a-causes-hepatic-stellate-cell-activation-via-the-induction-of-tnf%C3%AE-%C3%AE%C2%BA%C3%AE-%C3%AE-tgf%C3%AE-in-kupffer-cells
#14
Foteini Kiagiadaki, Marilena Kampa, Argyro Voumvouraki, Elias Castanas, Elias Kouroumalis, George Notas
Background&Aims. TGFβ superfamily member Activin-A is a multifunctional hormone/cytokine expressed in multiple tissues and cells., where it regulates cellular differentiation, proliferation, inflammation and tissue architecture. High activin-A levels have been reported in alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH). Our aim was to identify the cell types involved in the fibrotic processes induced by activin-A in liver and verify the liver diseases that this molecule can be found increased...
December 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29286155/mesenchymal-stem-cells-reverse-high%C3%A2-fat-diet%C3%A2-induced-non%C3%A2-alcoholic-fatty-liver-disease-through-suppression-of-cd4-t-lymphocytes-in-mice
#15
Huafeng Wang, Huan Zhang, Biao Huang, Guolin Miao, Xiaoyan Yan, Gang Gao, Yongping Luo, Huize Chen, Wei Chen, Luhong Yang
Although the multipotency of mesenchymal stem cells (MSCs) makes them an attractive choice for clinical applications, immune modulation is an important factor affecting MSC transplantation. At present, the effect of treatment with MSCs on non‑alcoholic fatty liver disease (NAFLD) has received little attention. In the present study, a compact bone‑derived method was used to isolate mouse MSCs (mMSCs) and a high‑fat diet was used to establish a mouse model of NAFLD. Immunophenotypic features of mMSCs were analyzed using flow cytometry...
December 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29286082/ccn1-cyr61-enhances-the-function-of-hepatic-stellate-cells-in-promoting-the-progression-of-hepatocellular-carcinoma
#16
Zhi-Qiang Li, Wei-Ru Wu, Chen Zhao, Chen Zhao, Xiao-Li Zhang, Zhong Yang, Jing Pan, Wei-Ke Si
Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)‑producing cells in liver fibrosis. Activated HSCs stimulate the proliferation and migration of hepatocellular carcinoma (HCC) cells. Cysteine‑rich 61 (CCN1/Cyr61) is an ECM protein. Our previous studies demonstrated that the expression of CCN1 was significantly higher in benign hepatic cirrhosis tissue and cancer‑adjacent hepatic cirrhosis tissues. CCN1 is a target gene of β‑catenin in HCC and promotes the proliferation of HCC cells...
December 29, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285255/agrin-para-secreted-by-pdgf-activated-human-hepatic-stellate-cells-promotes-hepatocarcinogenesis-in-vitro-and-in-vivo
#17
Xing Lv, Cheng Fang, Ruozhe Yin, Bowei Qiao, Runze Shang, Jianlin Wang, Wenjie Song, Yong He, Yong Chen
Evaluating the process and mechanism of fibrogenesis is essential in hepatocellular carcinoma (HCC), especially in hepatocyte transformation and oncogenic signaling. We evaluated the oncogenic role of agrin secreted by platelet-derived growth factor (PDGF)-induced hepatic stellate cell (HSC) in HCC. Cells were co-cultured to investigate the effect of activated HSC on hepatocytes. Liquid chromatography and protein profiling analysis were used to search the distinct proteins secreted in HSC supernatant. Sprague Dawley rats with Diethylnitrosamine (DEN)-induced HCC were used to simulate human liver cancer and sorafenib was administered to investigate its effect on hepatocarcinogenesis...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281671/short-telomere-length-in-ipf-lung-associates-with-fibrotic-lesions-and-predicts-survival
#18
Reinier Snetselaar, Aernoud A van Batenburg, Matthijs F M van Oosterhout, Karin M Kazemier, Suzan M Roothaan, Ton Peeters, Joanne J van der Vis, Roel Goldschmeding, Jan C Grutters, Coline H M van Moorsel
Telomere maintenance dysfunction has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). However, the mechanism of how telomere length is related to fibrosis in the lungs is unknown. Surgical lung biopsies of IPF patients typically show a heterogeneous pattern of non-fibrotic and fibrotic areas. Therefore, telomere length (TL) in both lung areas of patients with IPF and familial interstitial pneumonia was compared, specifically in alveolar type 2 (AT2) cells. Fluorescent in situ hybridization was used to determine TL in non-fibrotic and fibrotic areas of 35 subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29273418/pirfenidone-protects-against-paraquat-induced-lung-injury-and-fibrosis-in-mice-by-modulation-of-inflammation-oxidative-stress-and-gene-expression
#19
Fateme Pourgholamhosein, Rokhsana Rasooli, Mostafa Pournamdari, Leyla Pourgholi, Mitra Samareh-Fekri, Mahmoud Ghazi-Khansari, Maryam Iranpour, Hamid-Reza Poursalehi, Mahmoud-Reza Heidari, Ali Mandegary
In this study we investigated the protective effects and possible mechanisms of pirfenidone (PF) in paraquat (PQ)-induced lung injury and fibrosis in mice. Lung injury was induced by injection of PQ (20 mg/kg). Thereafter, mice orally received water and PF (100 and 200 mg/kg) for four weeks. After 28 days, the inflammation and fibrosis were determined in the lungs by analysis of histopathology, bronchoalveolar lavage fluid (BALF) cell count, lung wet/dry weight ratio, hydroxyproline content, and oxidative stress biomarkers...
December 19, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29261670/human-intrahepatic-ilc2-are-il-13positive-amphiregulinpositive-and-their-frequency-correlates-with-model-of-end-stage-liver-disease-score
#20
Hannah C Jeffery, Patrick McDowell, Philipp Lutz, Rebecca E Wawman, Sheree Roberts, Chris Bagnall, Jane Birtwistle, David H Adams, Ye Htun Oo
INTRODUCTION: Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. METHODS: Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function...
2017: PloS One
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