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https://www.readbyqxmd.com/read/28928802/baicalin-and-baicalein-attenuate-renal-fibrosis-in-vitro-via-inhibition-of-the-tgf-%C3%AE-1-signaling-pathway
#1
Qin Hu, Lina Gao, Bo Peng, Xinmin Liu
Baicalin and baicalein are flavonoid compounds derived from Scutellaria baicalensis Georgi. These compounds have been used in the treatment of numerous diseases, including fibrotic diseases. However, research regarding their antifibrotic effects and mechanism of action in renal fibrosis is limited. In the present study, normal rat kidney interstitial fibroblast (NRK-49F) cells were stimulated with transforming growth factor (TGF)-β1, with or without baicalin/baicalein, and assessed for proliferation, apoptosis, extracellular matrix (ECM) accumulation, collagen expression, TGF-β1 expression and mothers against decapentaplegic homolog 3 (SMAD3) protein activation...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28926478/characterization-of-spontaneous-hydrocephalus-development-in-the-young-atherosclerosis-prone-mice
#2
Chuanguo Liu, Guorong Li, Pingping Wang, Yan Wang, Jie Pan
Little has been reported on whether abnormal lipid metabolism affects hydrocephalus, although congenital malformations and infectious diseases are major causal factors for hydrocephalus development. In a study on the pathogenesis of atherogenesis in mice, we unexpectedly discovered that hydrocephalus occurred in partial apolipoptotein E (apoE) and low-density lipoprotein receptor (LDLR) double-knockout (apoE/LDLR) mice fed either chow or a high-fat and high-cholesterol diet between the ages of 4 and 12 weeks...
September 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#3
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/28919801/transforming-growth-factor-%C3%AE-1-smad3-independent-epithelial-mesenchymal-transition-in-type-i-collagen-glomerulopathy
#4
Amanda C Brodeur, Anna M Roberts-Pilgrim, Kimberlee L Thompson, Craig L Franklin, Charlotte L Phillips
The glomerulofibrotic Col1a2-deficient mouse model demonstrates glomerular homotrimeric type I collagen deposition in mesangial and subendothelial spaces. In this report, we investigate the role of transforming growth factor β1 (TGF-β1) in myofibroblast activation and epithelial-mesenchymal transition (EMT) in this glomerulopathy. Immunohistochemical analyses of glomerular α-sma, desmin, vimentin, and proliferating cell nuclear antigen demonstrated parietal epithelial cell proliferation and EMT in late stages of the glomerulopathy in the Col1a2-deficient mice...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28918914/analysis-of-genomes-and-transcriptomes-of-hepatocellular-carcinomas-identifies-mutations-and-gene-expression-changes-in-the-transforming-growth-factor-beta-pathway-short-title-prognostic-significance-of-tgf-%C3%AE-signature-in-liver-cancer
#5
Jian Chen, Sobia Zaidi, Shuyun Rao, Jiun-Sheng Chen, Liem Phan, Patrizia Farci, Xiaoping Su, Kirti Shetty, Jon White, Fausto Zamboni, Xifeng Wu, Asif Rashid, Nagarajan Pattabiraman, Raja Mazumder, Anelia Horvath, Ray-Chang Wu, Shulin Li, Cuiying Xiao, Chu-Xia Deng, David A Wheeler, Bibhuti Mishra, Rehan Akbani, Lopa Mishra
BACKGROUND & AIMS: Development of hepatocellular carcinoma (HCC) is associated with alterations in the transforming growth factor beta (TGFβ) signaling pathway, which regulates liver inflammation and can have tumor suppressor or promoter activities. Little is known about the roles of specific members of this pathway at specific of HCC development. We took an integrated approach to identify and validate the effects of changes in this pathway in HCC and identify therapeutic targets. METHODS: We performed transcriptome analyses for a total of 488 HCCs that include data from The Cancer Genome Atlas...
September 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28912732/transcriptome-identified-lncrnas-associated-with-renal-fibrosis-in-uuo-rat-model
#6
Jiazeng Sun, Shang Zhang, Bianhua Shi, Dexian Zheng, Juan Shi
Renal fibrosis represents a final common outcome of many renal diseases and has attracted a great deal of attention. To better understand whether lncRNAs could be a player in this process or be a biomarker for renal fibrosis diagnosis, we compared transcriptome sequencing data on renal tissues and urine respectively between UUO (unilateral ureteral obstruction) and shamed (Sham) rat model. Numerous genes including lncRNAs with significant changes in their expression were identified. 24 lncRNAs were up-regulated and 79 lncRNAs were down-regulated in the renal tissues of the UUO rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28903395/tgf-%C3%AE-2-induced-angptl4-expression-promotes-tumor-progression-and-osteoclast-differentiation-in-giant-cell-tumor-of-bone
#7
Bo Li, Ming Qian, Hao Cao, Qi Jia, Zhipeng Wu, Xinghai Yang, Tianyi Ma, Haifeng Wei, Tianrui Chen, Jianru Xiao
Although emerging studies have implicated that Aiopoietin-like 4 Protein (ANGPTL4) is related to the aggressiveness and metastasis of many tumors, the role of ANGPLT4 in giant cell tumor (GCT) of bone was rarely investigated. The mechanism of ANGPLT4 in tumor-induced osteoclastogenesis still remains unclear. In this study, we first demonstrated that ANGPTL4 was highly expressed in GCT compared to normal tissues, while we showed that TGF-β2 released by osteoclasts induced bone resorption could increase the expression of ANGPTL4 in GCTSCs...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903379/extracorporeal-shock-wave-treatment-attenuated-left-ventricular-dysfunction-and-remodeling-in-mini-pig-with-cardiorenal-syndrome
#8
Jiunn-Jye Sheu, Hani E E Ali, Ben-Chung Cheng, Hsin-Ju Chiang, Pei-Hsun Sung, Kuan-Hung Chen, Chih-Chao Yang, Yen-Ta Chen, John Y Chiang, Pao-Yuan Lin, Sarah Chua, Han-Tan Chai, Sheng-Ying Chung, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomly divided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903339/ing5-knockdown-enhances-migration-and-invasion-of-lung-cancer-cells-by-inducing-emt-via-egfr-pi3k-akt-and-il-6-stat3-signaling-pathways
#9
Xin-Li Liu, Xu-Tao Zhang, Jin Meng, Hong-Fei Zhang, Yong Zhao, Chen Li, Yang Sun, Qi-Bing Mei, Feng Zhang, Tao Zhang
ING5 belongs to the Inhibitor of Growth (ING) candidate tumor suppressor family, whose functions have been involved in the regulation of chromatin remodeling, cell cycle progression, proliferation and apoptosis. Our previous study has shown that ING5 overexpression inhibits lung cancer aggressiveness via suppressing epithelial to mesenchymal transition (EMT). However, the mechanisms remain largely unknown. In the current study, by Phospho-Kinase array and western blot, we have defined significantly upregulated EGFR/PI3K/Akt and IL-6/STAT3 oncogenic signaling pathways in ING5 knockdown A549 cells, which could be downregulated by ING5 overexpression...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901520/puerarin-promotes-the-viability-and-differentiation-of-mc3t3%C3%A2-e1-cells-by-mir%C3%A2-204%C3%A2-regulated-runx2-upregulation
#10
Xiu-Qin Zhan, Xiang-Wei Zeng, Ying-Ying Zhang, Qian Feng, Feng-Ming Zhao, Ze-Qun Jiang, Chao Sun
Puerarin has attracted increasing attention because of its beneficial effects on anti‑osteoporosis, but the molecular mechanisms underlying its actions on osteoblasts are not fully understood. The current study aimed to investigate the effect of puerarin on the cell viability and differentiation of mouse MC3T3‑E1 osteoblast‑like cells in vitro and its underlying mechanisms. The results indicated that 0.01, 0.1 and 1 mg/ml puerarin significantly promoted the viability of osteoblasts, enhanced alkaline phosphatase (ALP) activity and increased the expression of transforming growth factor‑β1, Smad2, Smad3 and Runt‑related transcription factor (Runx)2...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901475/valproic-acid-inhibits-epithelial%C3%A2-mesenchymal-transition-in-renal-cell-carcinoma-by-decreasing-smad4-expression
#11
Shaowei Mao, Guoliang Lu, Xiaopeng Lan, Chuanwei Yuan, Wei Jiang, Yougen Chen, Xunbo Jin, Qinghua Xia
Renal cell carcinoma (RCC) is the most common malignancy in urogenital neoplasms worldwide. According to previous studies, valproic acid (VPA), an anticonvulsant drug, can suppress tumor metastasis and decrease the expression level of Mothers against decapentaplegic homolog 4 (SMAD4) and therefore may inhibit epithelial‑mesenchymal transition (EMT), which is responsible for cancer metastasis. However, the association between VPA, EMT and SMAD4 in RCC metastasis remains obscure. In the present study, it was demonstrated that in the RCC cell lines 786‑O and Caki‑1 treated with VPA, the neural (N)‑cadherin, vimentin and SMAD4 protein and mRNA levels were decreased, accompanied with an increase in expression of epithelial (E)‑cadherin...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901425/knockdown-of-fstl1-attenuates-hepatic-stellate-cell-activation-through-the-tgf%C3%A2-%C3%AE-1-smad3-signaling-pathway
#12
Hongye Shang, Xiangjin Liu, Hui Guo
Follistatin‑like 1 (Fstl1) is a secreted glycoprotein that belongs to the follistatin and SPARC (secreted protein, acidic and rich in cysteine) families and was identified to serve a critical role in lung fibrosis. However, the role of Fstl1 in liver fibrosis remains undefined. Therefore, the aim of the present study was to investigate the role of Fstl1 in liver fibrosis. The results indicated that Fstl1 was highly expressed in human hepatic fibrosis tissues and activated hepatic stellate cells (HSCs). Furthermore, knockdown of Fstl1effectively suppressed HSC proliferation and the protein expression levels of α‑SMA and collagen I in transforming growth factor (TGF)‑β1‑treated HSCs...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28898507/growth-differentiation-factor-15-predicts-advanced-fibrosis-in-biopsy-proven-non-alcoholic-fatty-liver-disease
#13
Bo Kyung Koo, Sung Hee Um, Dong Soo Seo, Sae Kyung Joo, Jeong Mo Bae, Jeong Hwan Park, Mee Soo Chang, Jung Ho Kim, Jieun Lee, Won-Il Jeong, Won Kim
BACKGROUND & AIMS: We explored whether growth differentiation factor 15 (GDF15) affects the histological severity of non-alcoholic fatty liver disease (NAFLD) independent of insulin resistance. METHODS: In a biopsy-proven NAFLD cohort, we measured serum GDF15 levels using enzyme-linked immunosorbent assays. RESULTS: Among 190 subjects (mean age, 53±14 years; men, 52.1%), 72 (men, 65.3%) and 78 (men, 44.9%) were diagnosed with biopsy-proven non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), respectively...
September 12, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28891814/fibroblast-specific-tgf-%C3%AE-smad2-3-signaling-underlies-cardiac-fibrosis
#14
Hadi Khalil, Onur Kanisicak, Vikram Prasad, Robert N Correll, Xing Fu, Tobias Schips, Ronald J Vagnozzi, Ruijie Liu, Thanh Huynh, Se-Jin Lee, Jason Karch, Jeffery D Molkentin
The master cytokine TGF-β mediates tissue fibrosis associated with inflammation and tissue injury. TGF-β induces fibroblast activation and differentiation into myofibroblasts that secrete extracellular matrix proteins. Canonical TGF-β signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression. However, the importance of TGF-β-Smad2/3 signaling in fibroblast-mediated cardiac fibrosis has not been directly evaluated in vivo. Here, we examined pressure overload-induced cardiac fibrosis in fibroblast- and myofibroblast-specific inducible Cre-expressing mouse lines with selective deletion of the TGF-β receptors Tgfbr1/2, Smad2, or Smad3...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28884513/tgf-%C3%AE-1-attenuated-branching-morphogenesis-of-embryonic-murine-submandibular-gland-through-smad3-activation
#15
P Gao, X-H Qiao, L-M Gou, Y Huang, Q-H Li, L-J Li, X-Y Wang, C-J Li
Transforming growth factor-β1 (TGF-β1) plays several crucial regulatory roles in multiple physiological and pathological processes. The aim of this work was to investigate the role of TGF-β1 in branching morphogenesis of salivary gland. We harvested and cultured submandibular salivary glands (SMGs) from murine embryos, which were then treated with exogenous TGF-β1, or its neutralized antibody, Smad3 inhibitor, or Smad3 small interfering RNA (siRNA). Our results suggested that TGF-β1 attenuated branching morphogenesis of embryonic murine SMG via Smad3 activation, thus playing a negative regulatory role in salivary gland development...
September 7, 2017: Anatomia, Histologia, Embryologia
https://www.readbyqxmd.com/read/28883618/cg200745-an-hdac-inhibitor-induces-anti-tumour-effects-in-cholangiocarcinoma-cell-lines-via-mirnas-targeting-the-hippo-pathway
#16
Dawoon E Jung, Soo Been Park, Kahee Kim, Chanyang Kim, Si Young Song
Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881845/gender-differences-in-fibrosis-remodeling-in-patients-with-long-standing-persistent-atrial-fibrillation
#17
Zhi Li, Zengwei Wang, Zongtao Yin, Yuji Zhang, Xiaodong Xue, Jinsong Han, Yan Zhu, Jian Zhang, Maximilian Y Emmert, Huishan Wang
The success rate of catheter ablation in atrial fibrillation (AF) is known to be lower in females than in males. However, while the exact mechanism for this phenomenon remains to be elucidated, tissue fibrosis may play an important role in this regard. It has been shown that fibrosis promotes AF and its recurrence, thereby substantially reducing the efficacy of catheter ablation in AF patients. Thus, we hypothesized that fibrosis may contribute to gender differences in the outcomes of AF catheter ablation. Here we systematically assessed pulmonary vein sleeves obtained from 166 patients with and without long-standing persistent-AF (LSP-AF) in order to identify gender-specific mechanistic differences in fibrosis remodeling of AF patients...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877884/aberrant-smad3-phosphoisoforms-in-cyst-lining-epithelial-cells-in-the-cpk-mouse-a-model-of-autosomal-recessive-polycystic-kidney-disease
#18
Taketsugu Hama, Koichi Nakanishi, Masashi Sato, Hironobu Mukaiyama, Hiroko Togawa, Yuko Shima, Masayasu Miyajima, Kandai Nozu, Shizuko Nagao, Hisahide Takahashi, Mayumi Sako, Kazumoto Iijima, Norishige Yoshikawa, Hiroyuki Suzuki
Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-β/Smad3 signaling is involved, however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L) and COOH terminal regions (pSmad3C) and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in TGF-β/Smad3 pathway are implicated in carcinomas...
September 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28874823/role-of-smad3-and-p38-signalling-in-cigarette-smoke-induced-cftr-and-bk-dysfunction-in-primary-human-bronchial-airway-epithelial-cells
#19
Juliette Sailland, Astrid Grosche, Nathalie Baumlin, John S Dennis, Andreas Schmid, Stefanie Krick, Matthias Salathe
Mucociliary clearance (MCC) is a major airway host defence system that is impaired in patients with smoking-associated chronic bronchitis. This dysfunction is partially related to a decrease of airway surface liquid (ASL) volume that is in part regulated by apically expressed cystic fibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca(2+)-activated, and voltage dependent K(+) (BK) channels. Here, data from human bronchial epithelial cells (HBEC) confirm that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, thereby causing ASL depletion...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873458/anti-fibrotic-effects-of-valproic-acid-in-experimental-peritoneal-fibrosis
#20
Elerson C Costalonga, Luiza J de Freitas, Deise da S P Aragone, Filipe M O Silva, Irene L Noronha
BACKGROUND: Progressive fibrous thickening of the peritoneal membrane is a complication of long-term peritoneal dialysis (PD). TGF-β/Smad pathway activation, inflammation, and neoangiogenesis play important roles in peritoneal membrane (PM) changes induced by PD. Recently, histone deacetilase inhibitors (HDACi) have shown anti-fibrotic and anti-inflammatory effects in different experimental models. These drugs prevent deacetylation of histones causing a loosen chromatin, which in turn induce the expression of some anti-fibrotic genes...
2017: PloS One
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