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https://www.readbyqxmd.com/read/28716897/mcpip1-downregulation-in-clear-cell-renal-cell-carcinoma-promotes-vascularization-and-metastatic-progression
#1
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
<p>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL-6, IL-1 and IL-12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors, and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth and vascularity...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28713267/epoxyeicosatrienoic-acid-analog-decreases-renal-fibrosis-by-reducing-epithelial-to-mesenchymal-transition
#2
Melissa Skibba, Md Abdul Hye Khan, Lauren L Kolb, Michael M Yeboah, John R Falck, Radhika Amaradhi, John D Imig
Renal fibrosis, which is a critical pathophysiological event in chronic kidney diseases, is associated with renal epithelial-to-mesenchymal transition (EMT). Epoxyeicosatrienoic acids (EETs) are Cyp epoxygenase arachidonic acid metabolites that demonstrate biological actions that result in kidney protection. Herein, we investigated the ability of 14,15-EET and its synthetic analog, EET-A, to reduce kidney fibrosis induced by unilateral ureter obstruction (UUO). C57/BL6 male mice underwent sham or UUO surgical procedures and were treated with 14,15-EET or EET-A in osmotic pump (i...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28707079/down-regulation-of-mir-23a-inhibits-high-glucose-induced-emt-and-renal-fibrogenesis-by-up-regulation-of-snon
#3
Haiping Xu, Fuyun Sun, Xiuli Li, Lina Sun
It has been reported that transforming growth factor-β1 (TGF-β1) signaling plays an important role in the development of diabetic nephropathy (DN). The nuclear transcription co-repressor Ski-related novel protein N (SnoN) is a critical negative regulator of TGF-β1/Smad signal pathway, involving in tubule epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and tubulointerstitial fibrosis. In this study, we focused on miR-23a as a regulator of SnoN. Our purpose is to study the effects of miR-23a on high glucose (HG)-induced EMT process and ECM deposition in HK2 cells...
July 13, 2017: Human Cell
https://www.readbyqxmd.com/read/28701694/defective-cftr-leads-to-aberrant-%C3%AE-catenin-activation-and-kidney-fibrosis
#4
Jie Ting Zhang, Yan Wang, Jun Jiang Chen, Xiao Hu Zhang, Jian Da Dong, Lai Ling Tsang, Xiao Ru Huang, Zhiming Cai, Hui Yao Lan, Xiao Hua Jiang, Hsiao Chang Chan
Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl(-) channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT) and kidney fibrosis...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697727/intermedin-attenuates-renal-fibrosis-by-induction-of-heme-oxygenase-1-in-rats-with-unilateral-ureteral-obstruction
#5
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yufeng Qiao, Yun Fan, Zhiqiang Peng
BACKGROUND: Intermedin [IMD, adrenomedullin-2 (ADM-2)] attenuates renal fibrosis by inhibition of oxidative stress. However, the precise mechanisms remain unknown. Heme oxygenase-1 (HO-1), an antioxidant agent, is associated with antifibrogenic effects. ADM is known to induce HO-1. Whether IMD has any effect on HO-1 is unclear. Herein, we determined whether the antifibrotic properties of IMD are mediated by induction of HO-1. METHODS: Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on male Wistar rats...
July 11, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#6
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28667820/human-umbilical-cord-derived-mesenchymal-stem-cells-conditioned-medium-attenuate-interstitial-fibrosis-and-stimulate-the-repair-of-tubular-epithelial-cells-in-an-irreversible-model-of-unilateral-ureteral-obstruction
#7
Bo Liu, Feng-Xia Ding, Yang Liu, Geng Xiong, Tao Lin, Da-Wei He, Yuan-Yuan Zhang, De-Ying Zhang, Guang-Hui Wei
AIM: The growing number of patients suffering from chronic renal disease (CKD) is a challenge for the development of innovative therapies. Researchers have studied the therapeutic effects of cell therapy in acute kidney injury (AKI). However, the therapeutical effect of conditional medium (CM) in the CKD models have been rarely reported. Here, we examined the effects of umbilical cord derived-mesenchymal stem cells (hUC-MSCs) CM on renal fibrosis in a rat model of unilateral ureteral obstruction (UUO)...
July 1, 2017: Nephrology
https://www.readbyqxmd.com/read/28656288/vascular-endothelial-growth-inhibitor-174-and-its-functional-domains-inhibit-epithelial-mesenchymal-transition-in-renal-cell-carcinoma-cells-in%C3%A2-vitro
#8
Ning Zhang, Baoan Hong, Wenyong Lian, Changhua Zhou, Siqi Chen, Xin Du, Xiaohu Deng, Shayiremu Duoerkun, Qing Li, Yong Yang, Kan Gong
The present study was carried out to investigate the effects of vascular endothelial growth inhibitor 174 (VEGI174) and its functional domains (V7 and V8) on epithelial‑mesenchymal transition (EMT) in renal cell carcinoma (RCC) cells in vitro. The RCC cell lines A498 and 786‑O were used in this study. Based on our preliminary study, we selected full‑length VEGI174 and its functional domains (V7 and V8) as the target genes in this study. Plasmids containing VEGI174, V7 or V8 transgenes were constructed and transfected into A498 and 786‑O cell lines...
June 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#9
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28638433/shenqiwan-ameliorates-renal-fibrosis-in-rats-by-inhibiting-tgf-%C3%AE-1-smads-signaling-pathway
#10
Hongshu Chen, Yiqing Xu, Yuanxiao Yang, Xiaojie Zhou, Shijie Dai, Changyu Li
Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28627391/low-molecular-weight-fucoidan-and-its-fractions-inhibit-renal-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-or-fgf-2
#11
Xinpeng Li, Xiaohong Li, Quanbin Zhang, Tingting Zhao
We investigated the renal protective effects of low molecular weight fucoidan (LMWF) and its two fractions (F0.5 and F1.0), which were extracted from Laminaria japonica, on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) in HK-2 human renal proximal tubular cells. Cell morphology and EMT markers (fibronectin and alpha-smooth muscle actin) demonstrated that cells treated with TGF-β1 or FGF-2 developed EMT to a significant extent...
June 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28626343/anti-osm-antibody-inhibits-tubulointerstitial-lesion-in-a-murine-model-of-lupus-nephritis
#12
Qingjuan Liu, Yunxia Du, Kejun Li, Wei Zhang, Xiaojuan Feng, Jun Hao, Hongbo Li, Shuxia Liu
The purpose of this study was to investigate the role of oncostatin M (OSM) in tubulointerstitial lesion (TIL) in lupus nephritis (LN). We found that OSM was highly expressed in the renal tissue of LN mice. OSM is one of the interleukin-6 cytokine family members. In order to clarify the role and mechanism of OSM in LN, mice with LN were treated with anti-OSM antibody or isotype antibody. We evaluated the tubular epithelial-mesenchymal transdifferentiation (EMT) by detecting the E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin (FN) expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28618421/identification-of-tisp40-as-an-essential-regulator-of-renal-tubulointerstitial-fibrosis-via-tgf-%C3%AE-smads-pathway
#13
Cheng-Cheng Xiao, Jie Zhang, Peng-Cheng Luo, Cong Qin, Yang Du, Jin-Zhuo Ning, Hai-Zhou Zheng
BACKGROUND: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. METHODS: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT) and the underlying molecular mechanisms in transforming growth factor-β (TGF-β)-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R) by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28616713/modulation-of-the-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-emt-mediated-by-p1-and-p2-purine-receptors-in-mdck-cells
#14
Mariachiara Zuccarini, Patricia Giuliani, Silvana Buccella, Valentina Di Liberto, Giuseppa Mudò, Natale Belluardo, Marzia Carluccio, Margherita Rossini, Daniele Filippo Condorelli, Michel Piers Rathbone, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio
Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling...
June 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28611663/epigenetic-modifications-to-h3k9-in-renal-tubulointerstitial-cells-after-unilateral-ureteric-obstruction-and-tgf-%C3%AE-1-stimulation
#15
Timothy D Hewitson, Stephen G Holt, Sven-Jean Tan, Belinda Wigg, Chrishan S Samuel, Edward R Smith
Introduction: Epigenetic regulation of fibrogenesis through post-translational histone modifications (marks) may be a key determinant of progression in renal disease. In this study, we examined the distribution and acquisition of histone 3 Lysine 9 (H3K9) marks after injury and stimulation with the pro-fibrotic cytokine TGF-β1. Our focus was on their presence in activated fibroblasts (myofibroblasts) and epithelial cells (epithelial-mesenchymal transition). Methods and Results: Immunofluorescent microscopy was used to examine global H3K9 acetylation (H3K9Ac) and tri-methylation (H3K9Me3) after unilateral ureteric obstruction (UUO) in mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28606242/-effects-of-microrna-145-on-epithelial-mesenchymal-transition-of-tgf-%C3%AE-1-induced-human-renal-proximal-tubular-epithelial-cells
#16
Hua Liu, Xiao-Jie He, Guo-Jun Li, Qing-Xiong Ding, Wan-Xia Liang, Juan Fan
OBJECTIVE: To investigate the effects of microRNA-145 (miR-145) on epithelial-mesenchymal transition (EMT) of TGF-β1-induced human renal proximal tubular epithelial (HK-2) cells. METHODS: The gene sequence of miR-145 was synthesized and cloned into pCMV-myc to construct recombinant plasmid pCMV-miR-145. HK-2 cells were divided into four groups: control (untreated), TGF-β1 (treated with TGF-β1), blank+TGF-β1 (treated with TGF-β1 after HK-2 cells transfected with blank plasmid) and miR-145+TGF-β1 (treated with TGF-β1 after HK-2 cells transfected with pCMV-miR-145 recombinant plasmid)...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28596300/clear-cell-renal-cell-carcinoma-is-linked-to-epithelial-to-mesenchymal-transition-and-to-fibrosis
#17
Lea Landolt, Øystein Eikrem, Philipp Strauss, Andreas Scherer, David H Lovett, Christian Beisland, Kenneth Finne, Tarig Osman, Mohammad M Ibrahim, Gro Gausdal, Lavina Ahmed, James B Lorens, Jean Paul Thiery, Tuan Zea Tan, Miroslav Sekulic, Hans-Peter Marti
Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq(®) Access library preparation protocol and TruSeq Small RNA library preparation kit...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28594240/dimethylarginine-dimethylaminohydrolase-1-deficiency-induces-the-epithelial-to-mesenchymal-transition-in-renal-proximal-tubular-epithelial-cells-and-exacerbates-kidney-damage-in-aged-and-diabetic-mice
#18
Linlin Shi, Chenyang Zhao, Hongyun Wang, Tong Lei, Shasha Liu, Jianwei Cao, Zhongbing Lu
AIMS: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Emerging evidence suggests that plasma ADMA accumulation and DDAH1 activity/expression reduction are linked to chronic kidney disease (CKD) pathology, but the mechanisms remain largely unknown. Here, we examined the role of ADMA/DDAH1 in the epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs), an important mechanism for the pathogenesis of renal fibrosis...
July 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28587386/socs3-overexpression-inhibits-advanced-glycation-end-product-induced-emt-in-proximal-tubule-epithelial-cells
#19
Lin Yu, Ying Zhang, Huimin Zhang, Yingtao Li
Diabetic nephropathy (DN) is among the most severe complications of diabetes mellitus, and may lead to end-stage renal disease. Sustained exposure to advanced glycation end products (AGEs) typically causes renal tubular epithelial cells (TECs) to suffer from an epithelial-to-mesenchymal transition (EMT). However, there remains no consensus regarding the mechanism underlying the cause of EMT in TECs as induced by AGEs. In the present study, we investigated the promotion of EMT in TECs by AGEs, and the activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28579116/sirt3-prevents-angiotensin-ii-induced-renal-tubular-epithelial-mesenchymal-transition-by-ameliorating-oxidative-stress-and-mitochondrial-dysfunction
#20
Ping He, Zhuoming Li, Zhongbao Yue, Hui Gao, Guoshuai Feng, Panxia Wang, Yi Huang, Wenwei Luo, Huiqi Hong, Liying Liang, Shaorui Chen, Peiqing Liu
Silent mating type information regulation 2 homolog 3 (SIRT3) is a major protective mediator that ameliorates oxidative stress and mitochondrial dysfunction, which are associated with the pathogenesis of epithelial-mesenchymal transition (EMT). The present study was aimed to investigate the potential role of SIRT3 in renal tubular EMT both in vitro and in vivo. Firstly, we showed that the expression of SIRT3 was repressed in angiotensin II-induced EMT. SIRT3 deficiency triggered EMT response, while over-expression of SIRT3 attenuated EMT response...
June 1, 2017: Molecular and Cellular Endocrinology
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