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Epithelial to mesenchymal transition and fibrosis

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https://www.readbyqxmd.com/read/27914030/active-compounds-extracted-from-extra-virgin-olive-oil-counteract-mesothelial-to-mesenchymal-transition-of-peritoneal-mesothelium-cells-exposed-to-conventional-peritoneal-dialysate-in-vitro-and-in-vivo-evidences
#1
S Lupinacci, G Toteda, D Vizza, A Perri, C Benincasa, A Mollica, A La Russa, P Gigliotti, F Leone, D Lofaro, M Bonofiglio, E Perri, R Bonofiglio
During peritoneal dialysis (PD), peritoneal mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype that, together with the inflammatory process, promotes tissue fibrosis and a failure of peritoneal membrane function. To date, there is no definitive treatment for the progressive thickening and angiogenesis of the peritoneal membrane associated with PD. In this study we tested, in vitro and in vivo, the ability of active compounds extracted from extra virgin olive oil (AC-EVOO) to counteract the mesothelial-to-mesenchymal transition process (MMT) observed in mesothelial cells chronically exposed to the conventional peritoneal dialysate (DL)...
December 2, 2016: Journal of Nephrology
https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#2
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27910776/molecular-pathology-of-malignant-transformation-of-oral-submucous-fibrosis
#3
Amit Chattopadhyay, Jay Gopal Ray
Oral submucous fibrosis (OSF) is prevalent mostly in Southeast Asia, particularly in the Indian subcontinent. Chewing betel nuts and betel leaves, with or without tobacco, has been associated with OSF. Betel quid contents including guvacine, arecoline, guvacoline, arecaidine, and chavibetol are considered to play an important part in the occurrence of OSF. Transformation of OSF to squamous cell carcinoma (SCC) is variable, but up to 13% conversion of OSF to SCC has been reported. Various genetic and molecular mechanisms impact the malignant transformation of OSF, causing changes in the cell cycle, DNA, keratinocytes, and keratin; tumor-cell proliferation and survival; angiogenesis; fibrosis through epithelial-mesenchymal transitions (EMTs), and tissue hypoxia...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27909731/hypoxia-drives-the-transition-of-human-dermal-fibroblasts-to-a-myofibroblast-like-phenotype-via-the-tgf-%C3%AE-1-smad3-pathway
#4
Bin Zhao, Hao Guan, Jia-Qi Liu, Zhao Zheng, Qin Zhou, Jian Zhang, Lin-Lin Su, Da-Hai Hu
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring...
December 1, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909724/hsp27-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation-through-the-smad3-and-erk-pathways
#5
Gang Wang, Hao Jiao, Jun-Nian Zheng, Xia Sun
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-β (TGF-β)...
November 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27906099/p311-induces-the-transdifferentiation-of-epidermal-stem-cells-to-myofibroblast-like-cells-by-stimulating-transforming-growth-factor-%C3%AE-1-expression
#6
Haisheng Li, Zhihui Yao, Weifeng He, Hongyan Gao, Yang Bai, Sisi Yang, Lu Zhang, Rixing Zhan, Jianglin Tan, Junyi Zhou, Masao Takata, Jun Wu, Gaoxing Luo
BACKGROUND: Epithelial to mesenchymal transition, especially to myofibroblasts, plays an important role in wound healing, fibrosis, and carcinogenesis. Epidermal stem cells (EpSCs) are responsible for epidermal renewal and wound re-epithelialization. However, it remains unclear whether and how EpSCs transdifferentiate into myofibroblasts or myofibroblast-like cells (MFLCs). Here, we provide the first evidence showing that P311 induces EpSC to MFLC transdifferentiation (EpMyT) via TGFβ1/Smad signaling...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27895584/induced-pluripotent-stem-cells-inhibit-bleomycin-induced-pulmonary-fibrosis-in-mice-through-suppressing-tgf-%C3%AE-1-smad-mediated-epithelial-to-mesenchymal-transition
#7
Yan Zhou, Zhong He, Yuan Gao, Rui Zheng, Xiaoye Zhang, Li Zhao, Mingqi Tan
Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS) cells have been considered as an ideal resource for stem cell-based therapy. Although, an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF)-β1 signaling pathway, and epithelial to mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27881486/lysine-63-ubiquitination-is-involved-in-the-progression-of-tubular-damage-in-diabetic-nephropathy
#8
Paola Pontrelli, Francesca Conserva, Massimo Papale, Annarita Oranger, Mariagrazia Barozzino, Grazia Vocino, Maria Teresa Rocchetti, Margherita Gigante, Giuseppe Castellano, Michele Rossini, Simona Simone, Luigi Laviola, Francesco Giorgino, Giuseppe Grandaliano, Salvatore Di Paolo, Loreto Gesualdo
The purpose of our study was to evaluate how hyperglycemia (HG) influences Lys63 protein ubiquitination and its involvement in tubular damage and fibrosis in diabetic nephropathy (DN). Gene and protein expression of UBE2v1, a ubiquitin-conjugating E2-enzyme variant that mediates Lys63-linked ubiquitination, and Lys63-ubiquitinated proteins increased in HK2 tubular cells under HG. Matrix-assisted laser desorption/ionization-time of flight/tandem mass spectrometry identified 30 Lys63-ubiquitinated proteins, mainly involved in cellular organization, such as β-actin, whose Lys63 ubiquitination increased under HG, leading to cytoskeleton disorganization...
October 24, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27878273/pi3k-akt-signaling-is-involved-in-the-pathogenesis-of-bleomycin%C3%A2-induced-pulmonary-fibrosis-via-regulation-of-epithelial%C3%A2-mesenchymal-transition
#9
Xiao-Ling Zhang, Rong-Ge Xing, Liang Chen, Chun-Rong Liu, Zhi-Gang Miao
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by chronic inflammation, fibroblast proliferation and extracellular matrix deposition. However, the molecular and cellular mechanisms underlying the pathogenesis of pulmonary fibrosis remain to be fully elucidated. The contribution of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway in fibrotic processes remains to be investigated. The aim of the present study was to investigate the role of the PI3K/Akt pathway in pulmonary fibrosis...
November 22, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27878256/melatonin-attenuates-tgf%C3%AE-1-induced-epithelial-mesenchymal-transition-in-lung-alveolar-epithelial-cells
#10
Na Yu, Yi-Tian Sun, Xin-Ming Su, Miao He, Bing Dai, Jian Kang
Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease. However, the pathogenesis remains to be fully elucidated. Melatonin is secreted by the pineal gland, it has a strong antioxidant effect, and exerts an anti-fibrosis effect. Whether melatonin attenuates pulm -onary fibrosis by inhibiting epithelial‑mesenchymal transition (EMT) requires further research. The present study aimed to investigate whether melatonin prevents transforming growth factor‑β1 (TGF‑β1)‑induced EMT and underlying signaling pathways using reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunofluorescence...
November 16, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27876854/mir-706-inhibits-the-oxidative-stress-induced-activation-of-pkc%C3%AE-taok1-in-liver-fibrogenesis
#11
Ruili Yin, Duo Guo, Shuxian Zhang, Xiuying Zhang
Oxidative stress induces the activation of liver fibrogenic cells (myofibroblasts), thus promoting the expression of fibrosis-related genes, leading to hepatic fibrogenesis. MicroRNAs (miRNAs) are a new class of small RNAs ~18-25 nucleotides in length involved in post-transcriptional regulation of gene expression. Wound-healing and remodeling processes in liver fibrosis have been associated with changes in hepatic miRNA expression. However, the role of miR-706 in liver fibrogenesis is currently unknown. In the present study, we show that miR-706 is abundantly expressed in hepatocytes...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27874055/the-coordinated-roles-of-mir-26a-and-mir-30c-in-regulating-tgf%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-diabetic-nephropathy
#12
Zongji Zheng, Meiping Guan, Yijie Jia, Dan Wang, Ruoyu Pang, Fuping Lv, Zhizhou Xiao, Ling Wang, Hongbin Zhang, Yaoming Xue
MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27855406/scoparone-protects-against-pancreatic-fibrosis-via-tgf-%C3%AE-smad-signaling-in-rats
#13
Min Xu, Jing Cai, Hong Wei, Meng Zhou, Ping Xu, Hongmei Huang, Wanxin Peng, Fengyi Du, Aihua Gong, Youli Zhang
BACKGROUND/AIMS: This study was to investigate the influence of scoparone on pancreatic fibrosis in vitro and in vivo. METHODS: Pancreatic stellate cells (PSCs) were isolated from pancreas tissue blocks, and cultured for 3-5 generations for the experiment. PSCs were treated with scoparone in different doses as experimental groups, salvianolic acid B as a positive control and PBS as a blank group. We measured the effects of scoparone on cellular proliferation, oxidative stress, epithelial-mesenchymal transition (EMT), and pancreatic fibrosis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27855304/therapeutic-activity-of-the-histone-deacetylase-inhibitor-sb939-on-renal-fibrosis
#14
Sun-Woo Kang, Soung-Min Lee, Joo-Yong Kim, So-Yeon Kim, Yeong-Hoon Kim, Tae-Hee Kim, Mi-Seon Kang, Won-Hee Jang, Su-Kil Seo
Fibrosis is the final pathological outcome of many chronic kidney diseases and is quite common. Thus, development of effective anti-fibrotic agents is urgently needed. Although histone deacetylases (HDACs) have been reported to be involved in renal fibrosis, current HDAC inhibitors are unsatisfactory anti-fibrosis drugs. Therefore, more potentially relevant anti-renal fibrosis HDAC inhibitors are needed. We initially found that non-cytotoxic concentrations of SB939 (pracinostat) had strong anti-fibrotic activity, drastically decreasing TGF-β1-induced alpha smooth muscle actin (α-SMA) expression in the NRK renal fibroblast cell line...
November 14, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27855278/cadherin-11-is-a-cell-surface-marker-up-regulated-in-activated-pancreatic-stellate-cells-and-is-involved-in-pancreatic-cancer-cell-migration
#15
Chiara Birtolo, Hung Pham, Susan Morvaridi, Chintan Chheda, Vay Liang W Go, Andrzej Ptasznik, Mouad Edderkaoui, Michael Weisman, Erika Noss, Michael Brenner, Brent Larson, Maha Guindi, Qiang Wang, Stephen J Pandol
Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined...
November 14, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27829579/curcumin-suppresses-epithelial-mesenchymal-transition-of-renal-tubular-epithelial-cells-through-the-inhibition-of-akt-mtor-pathway
#16
Fang-Qiang Zhu, Min-Jia Chen, Ming Zhu, Rong-Seng Zhao, Wei Qiu, Xiang Xu, Hong Liu, Hong-Wen Zhao, Rong-Jie Yu, Xiong-Fei Wu, Keqin Zhang, Hong Huang
Curcumin has exhibited a protective effect against development of renal fibrosis in animal models, however, its underlying molecular mechanisms are largely unclear. Therefore, we investigated the anti-fibrosis effects of curcumin in TGF-β1-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the PI3K/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-β1 or curcumin alone, or TGF-β1 in combination with curcumin. The effect of curcumin on cell proliferation was measured by MTT assay...
November 8, 2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27816946/advanced-glycation-end-products-mediated-cellular-and-molecular-events-in-the-pathology-of-diabetic-nephropathy
#17
Anil Kumar Pasupulati, P Swathi Chitra, G Bhanuprakash Reddy
Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs)...
November 7, 2016: Biomolecular Concepts
https://www.readbyqxmd.com/read/27796696/klotho-mitigates-cyclosporine-a-csa-induced-epithelial-mesenchymal-transition-emt-and-renal-fibrosis-in-rats
#18
Qi-Feng Liu, Jian-Ming Ye, Li-Xia Yu, Xiao-Hong Dong, Jian-Hua Feng, Yan Xiong, Xiao-Xia Gu, Sha-Sha Li
PURPOSE: Klotho deficiency is implicated in various kidney diseases, including renal fibrosis. The aim of this study was to investigate the effect of Klotho administration on epithelial-mesenchymal transition (EMT) and renal fibrosis induced by cyclosporine A (CsA) in rats. METHODS: CsA-induced renal fibrosis was established by oral administration of CsA (30 mg/kg) to rats on a low-salt diet for 28 days. Klotho was administered to rats by intraperitoneal injection...
October 28, 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27793799/brd4-mediates-nf%C3%AE%C2%BAb-dependent-epithelial-mesenchymal-transition-and-pulmonary-fibrosis-via-transcriptional-elongation
#19
Bing Tian, Yingxin Zhao, Hong Sun, Yueqing Zhang, Jun Yang, Allan R Brasier
Chronic epithelial injury triggers a TGFβ-mediated cellular transition from normal epithelium into a mesenchymal-like state that produces subepithelial fibrosis and airway remodeling. Here we examined how TGFβ induces the mesenchymal cell state, and determined its mechanism. We observe that TGFβ stimulation activates an inflammatory gene program controlled by the NFκB/RelA signaling pathway. In the mesenchymal state, NFκB-dependent immediate-early genes accumulate euchromatin marks and processive RNA polymerase...
October 28, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27791279/rar-related-orphan-receptor-gamma-ror-%C3%AE-mediates-epithelial-mesenchymal-transition-of-hepatocytes-during-hepatic-fibrosis
#20
Sung Min Kim, Jung Eun Choi, Wonhee Hur, Jung-Hee Kim, Sung Woo Hong, Eun Byul Lee, Joon Ho Lee, Tian Zhu Li, Pil Soo Sung, Seung Kew Yoon
The epithelial-mesenchymal transition (EMT) is involved in many different types of cellular behavior, including liver fibrosis. In this report, we studied a novel function of RAR-related orphan receptor gamma (ROR-γ) in hepatocyte EMT during liver fibrosis. To induce EMT in vitro, primary hepatocytes and FL83B cells were treated with TGF-β1. Expression of ROR-γ was analyzed by western blot in the fibrotic mouse livers and human livers with cirrhosis. To verify the role of ROR-γ in hepatocyte EMT, we silenced ROR-γ in FL83B cells using a lentiviral short hairpin RNA (shRNA) vector...
October 28, 2016: Journal of Cellular Biochemistry
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