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Fibrogenesis

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https://www.readbyqxmd.com/read/28542443/effects-of-pressure-support-and-pressure-controlled-ventilation-on-lung-damage-in-a-model-of-mild-extrapulmonary-acute-lung-injury-with-intra-abdominal-hypertension
#1
Cintia L Santos, Raquel S Santos, Lillian Moraes, Cynthia S Samary, Nathane S Felix, Johnatas D Silva, Marcelo M Morales, Robert Huhle, Marcelo G Abreu, Alberto Schanaider, Pedro L Silva, Paolo Pelosi, Patricia R M Rocco
Intra-abdominal hypertension (IAH) may co-occur with the acute respiratory distress syndrome (ARDS), with significant impact on morbidity and mortality. Lung-protective controlled mechanical ventilation with low tidal volume and positive end-expiratory pressure (PEEP) has been recommended in ARDS. However, mechanical ventilation with spontaneous breathing activity may be beneficial to lung function and reduce lung damage in mild ARDS. We hypothesized that preserving spontaneous breathing activity during pressure support ventilation (PSV) would improve respiratory function and minimize ventilator-induced lung injury (VILI) compared to pressure-controlled ventilation (PCV) in mild extrapulmonary acute lung injury (ALI) with IAH...
2017: PloS One
https://www.readbyqxmd.com/read/28540451/exogenous-cgrp-upregulates-profibrogenic-growth-factors-through-pkc-jnk-signaling-pathway-in-kidney-proximal-tubular-cells
#2
Sang Pil Yoon, Jinu Kim
Kidney denervation prevents the development of tubulointerstitial fibrosis, but the neuropeptide calcitonin gene-related peptide (CGRP) in the denervated kidneys restores the fibrotic feature through the upregulation of profibrogenic growth factors. CGRP is involved in aggravation of inflammation by increasing the number of circulating cells and chemotactic factors. However, it is not clear how CGRP contributes to the upregulation of profibrogenic factors during fibrogenesis. In both human and pig kidney proximal tubular cell lines, administration of 1 nM CGRP significantly increased the levels of transforming growth factor-β1 (TGF-β1) production and connective tissue growth factor (CTGF) expression at 6 and 24 h after the administration...
May 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28538876/combination-therapy-with-butyrate-and-docosahexaenoic-acid-for-keloid-fibrogenesis-an-in-vitro-study
#3
Kazuhiro Torii, Noriaki Maeshige, Michiko Aoyama-Ishikawa, Makoto Miyoshi, Hiroto Terashi, Makoto Usami
Background: A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action. Objective: In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28535799/the-spleen-in-liver-cirrhosis-revisiting-an-old-enemy-with-novel-targets
#4
REVIEW
Liang Li, Mubing Duan, Weisan Chen, An Jiang, Xiaoming Li, Jun Yang, Zongfang Li
The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration...
May 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28534985/microarray-analysis-of-differentially-expressed-genes-in-l929-mouse-fibroblast-cells-exposed-to-leptin-and-hypoxia
#5
Ping Ouyang, Sen Wang, He Zhang, Zhigang Huang, Pei Wei, Ye Zhang, Zhuguo Wu, Tao Li
Leptin and hypoxia are pro-fibrotic factors involved in fibrogenesis, however, the gene expression profiles remain to be fully elucidated. The aim of the present study was to investigate the regulatory roles of leptin and hypoxia on the L929 mouse fibroblast cell line. The cells were assigned to a normoxia, normoxia with leptin, hypoxia, and hypoxia with leptin group. The cDNA expression was detected using an Agilent mRNA array platform. The differentially expressed genes (DEGs) in response to leptin and hypoxia were identified using reverse transcription‑quantitative polymerase chain reaction analysis, followed by clustering analysis, Gene Ontology analysis and pathway analysis...
May 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28525892/rasal1-is-a-potent-regulator-of-hepatic-stellate-cell-activity-and-liver-fibrosis
#6
Akemi Takata, Motoyuki Otsuka, Takahiro Kishikawa, Mari Yamagami, Rei Ishibashi, Kazuma Sekiba, Tatsunori Suzuki, Motoko Ohno, Yui Yamashita, Takaya Abe, Ryota Masuzaki, Tsuneo Ikenoue, Kazuhiko Koike
Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic liver injury. The transition of hepatic stellate cells (HSCs) from quiescent cells into proliferative and fibrogenic cells is a central event in liver fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase-activating protein, which switches off RAS activity, is significantly decreased during HSC activation, and that HSC activation can be antagonized by forced expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting with angiotensin II receptor, type 1...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520165/targeting-ccl4-induced-liver-fibrosis-by-rna-interference-mediated-inhibition-of-cyclin-e1-in-mice
#7
Jörg-Martin Bangen, Linda Hammerich, Roland Sonntag, Maike Baues, Ute Haas, Daniela Lambertz, Thomas Longerich, Twan Lammers, Frank Tacke, Christian Trautwein, Christian Liedtke
Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSC). Cyclin E1 (CcnE1) is the regulatory subunit of the Cyclin-dependent Kinase 2 (Cdk2) and controls cell cycle re-entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation and survival of HSC and protects from liver fibrogenesis. The aim of the present study was to translate these findings into pre-clinical applications using an RNAi-based approach...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28515040/a-systematic-review-of-overlapping-microrna-patterns-in-systemic-sclerosis-and-idiopathic-pulmonary-fibrosis
#8
REVIEW
Gianluca Bagnato, William Neal Roberts, Jesse Roman, Sebastiano Gangemi
Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome...
June 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28514653/the-presence-of-interleukin-13-at-pancreatic-adm-panin-lesions-alters-macrophage-populations-and-mediates-pancreatic-tumorigenesis
#9
Geou-Yarh Liou, Ligia Bastea, Alicia Fleming, Heike Döppler, Brandy H Edenfield, David W Dawson, Lizhi Zhang, Nabeel Bardeesy, Peter Storz
The contributions of the innate immune system to the development of pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear when and how this inflammatory macrophage population is replaced by tumor-promoting macrophages. Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28506744/hepatic-stellate-cells-as-key-target-in-liver-fibrosis
#10
Takaaki Higashi, Scott L Friedman, Yujin Hoshida
Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation...
May 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28498509/molecular-interplays-in-hepatic-stellate-cells-apoptosis-senescence-and-phenotype-reversion-as-cellular-connections-that-modulates-liver-fibrosis
#11
REVIEW
Silva B O, Ramos L F, Moraes K C M
Liver fibrosis is a pathophysiological process correlated with intense repair and cicatrization mechanisms in injured liver, and over the past few years, the characterization of the fine-tuning of molecular interconnections that support the development of liver fibrosis has been investigated. In this cellular process, the hepatic stellate cells (HSCs) support the organ fibrogenesis. The HSCs are found in two distinct morpho-physiological states: quiescent and activated. In normal liver, most HSCs are found in quiescent state, presenting a considerable amount of lipid droplets in the cytoplasm, while in injured liver the activated phenotype of HSCs is a myofibroblast,that secretes extracellular matrix elements and contributes to the establishment of the fibrotic process...
May 12, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28496142/src-homology-protein-tyrosine-phosphatase-1-agonist-sc-43-reduces-liver-fibrosis
#12
Tung-Hung Su, Chung-Wai Shiau, Ping Jao, Nian-Jie Yang, Wei-Tien Tai, Chun-Jen Liu, Tai-Chung Tseng, Hung-Chih Yang, Chen-Hua Liu, Kai-Wen Huang, Ting-Chen Hu, Yu-Jen Huang, Yao-Ming Wu, Li-Ju Chen, Pei-Jer Chen, Ding-Shinn Chen, Kuen-Feng Chen, Jia-Horng Kao
This study aimed to investigate the role of src-homology protein tyrosine phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3) pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1 activity, was evaluated in two fibrosis mouse models by carbon tetrachloride induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate cells (HSCs) were used for mechanistic investigations...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495857/tgf-%C3%AE-1-induces-fstl1-via-the-smad3-c-jun-pathway-in-lung-fibroblasts
#13
Xiaohong Zheng, Chao Qi, Si Zhang, Yinshan Fang, Wen Ning
Transforming growth factor (TGF)-β1 has long been regarded as a central mediator of tissue fibrosis. Follistatin-like 1 (Fstl1) is a crucial pro-fibrotic glycoprotein that is up-regulated in fibrotic lung tissues and that promotes fibrogenesis via facilitating TGF-β signaling. Here we examined the signaling pathway by which TGF-β1 up-regulates Fstl1 expression in mouse pulmonary fibroblasts. TGF-β1 regulated Fstl1 expression at both the transcriptional as well as translational levels. Transforming growth factor (TGF)-β1 has long been regarded as a central mediator of tissue fibrosis...
May 11, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28495592/mir-21-promotes-fibrogenesis-in-peritoneal-dialysis
#14
Melisa Lopez-Anton, Mark Lambie, Manuel Lopez-Cabrera, Claus P Schmitt, Vicente Ruiz-Carpio, Maria Bartosova, Betti Schaefer, Simon Davies, Timothy Stone, Robert Jenkins, Philip R Taylor, Nicholas Topley, Timothy Bowen, Donald Fraser
Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-β1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change...
May 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28488693/icos-protects-against-mortality-from-acute-lung-injury-through-activation-of-il-5-ilc2s
#15
C L Hrusch, S T Manns, D Bryazka, J Casaos, C A Bonham, M R Jaffery, K M Blaine, K A M Mills, P A Verhoef, A O Adegunsoye, J W Williams, M Y Tjota, T V Moore, M E Strek, I Noth, A I Sperling
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis...
May 10, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28486921/soluble-guanylate-cyclase-a-new-therapeutic-target-for-fibrotic-diseases
#16
Liqing Hu, Zeyu Wang, Rui Yi, Honghong Yi, Sijia Xiao, Zhuo Chen, Gaoyun Hu, Qianbin Li
Fibrosis occurs in a variety of organs and frequently brings great harm to patients, even contributes to their death. Despite great efforts made in the field of fibrosis over the past decades and considerable understanding of the pathogenesis of fibrotic reactions attained, there is still lack of effective anti-fibrotic treatments. A growing body of evidence indicates a significant anti-fibrotic potential of activated soluble guanylate cyclase (sGC), which emphasizes the importance of sGC in fibrogenesis of diverse organs including skin, kidney, liver and lung...
May 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28483378/c-myc-promotes-renal-fibrosis-by-inducing-integrin-%C3%AE-v-mediated-transforming-growth-factor-%C3%AE-signaling
#17
Yang Shen, Naijun Miao, Bao Wang, Jinlan Xu, Xinxin Gan, Dan Xu, Li Zhou, Hong Xue, Wei Zhang, Li Yang, Limin Lu
Fibrogenesis involves the activation of renal fibroblasts upon kidney injury. However, the mechanisms underlying renal fibroblast activation are poorly characterized. c-Myc is a predominant oncogene encoding a pleiotropic transcription factor that participates in the regulation of various genes, including genes vital for regulating the cell cycle, cell proliferation, and apoptosis. Here we tested whether renal fibrosis in unilateral ureteral obstruction and folic acid-induced renal fibrosis mouse models are associated with the overexpression of c-Myc...
May 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28482267/amelioration-of-ccl4-induced-liver-injury-in-rats-by-selenizing-astragalus-polysaccharides-role-of-proinflammatory-cytokines-oxidative-stress-and-hepatic-stellate-cells
#18
Mohammed Hamid, Dandan Liu, Yassin Abdulrahim, Yunhuan Liu, Gang Qian, Alamzeb Khan, Fang Gan, Kehe Huang
Selenizing Astragalus polysaccharides (sAPS) were prepared by nitric acid-sodium selenite method. Effect of sAPS on carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanisms were investigated in the rat. Forty male Wistar rats were divided into five equal groups as follows: control group; CCl4 group; CCl4+Astragalus polysaccharides group; CCl4+sodium selenite group and CCl4+selenizing Astragalus polysaccharides group. The results showed that sAPS significantly decreased the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase in the serum, malondialdehyde and hydroxyproline content in liver (P<0...
May 2, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28472963/experimental-approach-to-igf-1-therapy-in-ccl4-induced-acute-liver-damage-in-healthy-controls-and-mice-with-partial-igf-1-deficiency
#19
Luis A Morales-Garza, Juan E Puche, Gabriel A Aguirre, Úrsula Muñoz, Mariano García-Magariño, Rocío G De la Garza, Inma Castilla-Cortazar
BACKGROUND: Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl4)-induced liver damage compared to healthy controls (Wt Igf (+/+)). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 (+/-))...
May 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28472477/fibronectin-type-iii-domain-containing-protein-5-rs3480-a-g-polymorphism-irisin-and-liver-fibrosis-in-patients-with-nonalcoholic-fatty-liver-disease
#20
Salvatore Petta, Luca Valenti, Gianluca Svegliati-Baroni, Massimiliano Ruscica, Rosaria Maria Pipitone, Paola Dongiovanni, Chiara Rychlicki, Nicola Ferri, Calogero Cammà, Anna Ludovica Fracanzani, Irene Pierantonelli, Vito Di Marco, Marica Meroni, Debora Giordano, Stefania Grimaudo, Marco Maggioni, Daniela Cabibi, Silvia Fargion, Antonio Craxì
Context: Contrasting data have been reported on the role of irisin, a novel myokine encoded by the FNDC5 gene, in NAFLD pathogenesis. We tested in patients with suspected NASH the association of FNDC5 variants, hepatic expression and circulating irisin with liver damage(F2-F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods: We considered 593 consecutive patients, who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and without steatosis...
May 3, 2017: Journal of Clinical Endocrinology and Metabolism
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