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https://www.readbyqxmd.com/read/28186986/common-cytotoxic-chemotherapeutics-induce-epithelial-mesenchymal-transition-emt-downstream-of-er-stress
#1
Parag P Shah, Tess V Dupre, Leah J Siskind, Levi J Beverly
Endoplasmic reticulum (ER) in eukaryotes is a main organelle involved in a wide variety of functions including calcium storage, lipid biosynthesis, protein folding and protein transport. Disruption of ER homeostasis leads to ER stress and activation of the unfolded protein response (UPR). We and others have previously found that ER stress induces EMT in different cellular systems. Induction of ER stress with chemical modulators of ER homeostasis was sufficient to activate an EMT-like state in all cellular systems tested...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28163747/tangzhiqing-granules-alleviate-podocyte-epithelial-mesenchymal-transition-in-kidney-of-diabetic-rats
#2
Haiyan Xu, Xu Wang, Mingming Liu, Xueyuan He
This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28159470/hedgehog-pathway-plays-a-vital-role-in-hiv-induced-epithelial-mesenchymal-transition-of-podocyte
#3
Xiqian Lan, Hongxiu Wen, Kang Cheng, Andrei Plagov, Seyedeh Shadafarin Marashi Shoshtari, Ashwani Malhotra, Pravin C Singhal
HIV-associated nephropathy (HIVAN) is characterized by heavy proteinuria, rapidly progressive renal failure, and distinct morphological features in the kidney. HIV-induced epithelial-mesenchymal transition (EMT) is critically important for the progression of kidney injury. In this study, we tested the role of hedgehog pathway in the HIV-induced EMT and fibrosis of kidney. We used the Tg26 mice, the abundantly used HIVAN mouse model, to investigate the activation of hedgehog pathway by HIV. Western blotting and real time PCR results showed that renal tissue expression of hedgehog pathway related molecules, including hedgehog homologous (Shh, Ihh, Dhh), PTCH, and Gli1, were increased in HIVAN (Tg26) mice; while immunofluorescent staining displayed localization PTCH expression in podocytes...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28158902/metformin-attenuates-albumin-induced-alterations-in-renal-tubular-cells-in-vitro
#4
Soumaya Allouch, Shankar Munusamy
Proteinuria (albuminuria) plays a crucial role in the etiology of chronic kidney disease (CKD) via alteration of multiple signaling pathways and cellular process in renal cells. The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28120209/differential-proteomics-analysis-of-endometriosis-in-blood-stasis-syndrome
#5
Yi Wen, Yan Wang, Ting-Ting Feng, Shao-Bin Wei
OBJECTIVE: To investigate the innate characters of 3 endometriosis (EMT) syndromes, blood stasis (BS), qi stagnation and blood stasis (QSBS) as well as Shen (Kidney) deficiency and blood stasis (KDBS) in terms of proteomics, lay a molecular biological basis for the differentiation of various blood stasis syndromes of EMT, establish a EMT microscopic syndrome differentiation and diagnosis system in terms of proteomics, discover the evolution principles and therapeutic targets of these EMT syndromes, and search their significant molecular markers and genetic intervention targets...
January 24, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28115235/anti-fibrotic-effects-of-chronic-treatment-with-the-selective-fxr-agonist-obeticholic-acid-in-the-bleomycin-induced-rat-model-of-pulmonary-fibrosis
#6
Paolo Comeglio, Sandra Filippi, Erica Sarchielli, Annamaria Morelli, Ilaria Cellai, Francesca Corcetto, Chiara Corno, Elena Maneschi, Alessandro Pini, Luciano Adorini, Gabriella Barbara Vannelli, Mario Maggi, Linda Vignozzi
Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated...
January 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28106131/hif-1%C3%AE-induction-during-reperfusion-avoids-maladaptive-repair-after-renal-ischemia-reperfusion-involving-mir127-3p
#7
Elisa Conde, Sara Giménez-Moyano, Laura Martín-Gómez, Macarena Rodríguez, M Edurne Ramos, Elia Aguado-Fraile, Ignacio Blanco-Sanchez, Ana Saiz, María Laura García-Bermejo
Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092863/adipose-derived-stem-cells-ameliorate-renal-interstitial-fibrosis-through-inhibition-of-emt-and-inflammatory-response-via-tgf-%C3%AE-1-signaling-pathway
#8
Yan Song, Changliang Peng, Shasha Lv, Jing Cheng, Shanshan Liu, Qing Wen, Guangju Guan, Gang Liu
Adipose-derived stem cells (ADSCs) have been successfully used to treat acute kidney injury or acute renal failure. However, the effect of ADSCs on treating renal interstitial fibrosis remains unknown. Here, we assessed the therapeutic efficacy of ADSCs on renal interstitial fibrosis induced by unilateral ureter obstruction (UUO) and explored the potential mechanisms. After 7days of UUO, rats were injected with ADSCs (5×10(6)) or vehicle via tail vein. We found that ADSCs administration significantly ameliorated renal interstitial fibrosis, the occurrence of epithelial-mesenchymal transition (EMT) and inflammatory response...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28042546/tempol-effect-on-epithelial-mesenchymal-transition-induced-by-hyperglycemia
#9
Mohammad Jafari, Farahnaz Dadras, Hamid Reza Ghadimipour, Mohamad Ali Seif Rabiei, Farhad Khoshjou
BACKGROUND: One of common mechanisms in pathophysiology of chronic kidney diseases is epithelial-mesenchymal transition (EMT). On the other hand oxidative stress has been known to participate in kidney damage of diabetic nephropathy (DN). OBJECTIVES: We studied if tempol, a well-known antioxidant agent, can ameliorate EMT in DN induced in male rats. MATERIALS AND METHODS: Twenty-seven male rats were equally divided in to 4 groups. Group I (control or C), group II (diabetic or D), group III (T) rats which was given tempol (100 mg/kg/day) by gavages for 28 days and group IV (D&T) was diabetic rats that also received same dose of tempol...
January 2017: Journal of Nephropathology
https://www.readbyqxmd.com/read/27959449/mir-204-regulates-epithelial-mesenchymal-transition-by-targeting-sp1-in-the-tubular-epithelial-cells-after-acute-kidney-injury-induced-by-ischemia-reperfusion
#10
Shun-Jie Chen, Ping Wu, Li-Jing Sun, Bo Zhou, Wei Niu, Shuang Liu, Fu-Jun Lin, Geng-Ru Jiang
Acute kidney injury (AKI) is a disease where kidney function is lost almost instantaneously; it can develop very rapidly over few hours to maximum of few days. Despite the advent of technology, the clinical management against this disease is very poor, and most of the time it is life-threatening. AKI has been actively regulated by extracellular matrix proteins (ECM), however, its underlying mechanism of regulation during AKI progression is very poorly understood. In this study, we explored the integrated network of mRNA and microRNAs (miRNAs) that maintains the progression of ECM after induction of AKI by lethal ischemia...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27936102/am251-suppresses-epithelial-mesenchymal-transition-of-renal-tubular-epithelial-cells
#11
Tomoyo Yoshinaga, Kenichiro Uwabe, Shoichi Naito, Kenichi Higashino, Toru Nakano, Yoshito Numata, Akio Kihara
Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells...
2016: PloS One
https://www.readbyqxmd.com/read/27902771/piceatannol-attenuates-renal-fibrosis-induced-by-unilateral-ureteral-obstruction-via-downregulation-of-histone-deacetylase-4-5-or-p38-mapk-signaling
#12
Sin Young Choi, Zhe Hao Piao, Li Jin, Jung Ha Kim, Gwi Ran Kim, Yuhee Ryu, Ming Quan Lin, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong
Piceatannol, a resveratrol metabolite, is a phenolic compound found in red wine and grapes. We investigated the effect of piceatannol on renal fibrosis and histone deacetylase (HDAC) expression in a mouse model of unilateral ureteral obstruction (UUO). Fibrosis was established by UUO and piceatannol was intraperitoneally injected for 2 weeks. Piceatannol suppressed extracellular matrix (ECM) protein deposition including collagen type I and fibronectin as well as connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in UUO kidneys...
2016: PloS One
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
#13
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/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...
January 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27829579/curcumin-suppresses-epithelial-mesenchymal-transition-of-renal-tubular-epithelial-cells-through-the-inhibition-of-akt-mtor-pathway
#15
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 transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-β1 or curcumin alone, or TGF-β1 in combination with curcumin...
January 1, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27812180/comparative-gene-expression-profiling-of-primary-and-metastatic-renal-cell-carcinoma-stem-cell-like-cancer-cells
#16
Mohammed I Khan, Anna M Czarnecka, Sławomir Lewicki, Igor Helbrecht, Klaudia Brodaczewska, Irena Koch, Robert Zdanowski, Magdalena Król, Cezary Szczylik
BACKGROUND: Recent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells-stem cell-like cancer cells (SCLCCs)-which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells...
2016: PloS One
https://www.readbyqxmd.com/read/27796696/klotho-mitigates-cyclosporine-a-csa-induced-epithelial-mesenchymal-transition-emt-and-renal-fibrosis-in-rats
#17
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/27754026/yia-03-02-adiponectin-mediated-epithelial-autophagy-attenuates-hypertensive-renal-fibrosis
#18
Cheng-Chao Ruan, Yan Li, Yu Ma, Ding-Liang Zhu, Ping-Jin Gao
OBJECTIVE: Previous studies have indicated that adiponectin (APN) protects against hypertension-related cardiovascular disease. However, whether APN is involved in the regulation of hypertensive renal damage remains unclear. The present study aimed to elucidate how APN regulates renal epithelial to mesenchymal transdifferentiation (EMT) in desoxycorticosterone (DOCA)-salt hypertensive mice. DESIGN AND METHOD: Male APN knockout (APNKO) mice and wild-type (WT) C57BL/6 littermates were sc infused with DOCA pellet (50 mg for 21 day release)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27735870/a-high-content-screening-assay-to-identify-compounds-with-anti-epithelial-mesenchymal-transition-effects-from-the-chinese-herbal-medicine-tong-mai-yang-xin-wan
#19
Ningning Liu, Lailai Li, Xin Zhu, Zhiqiang Ling, Jianguo Feng, Ying Hu, Yi Wang, Lijun Mou, Yi Wang
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27707584/epithelial-mesenchymal-transition-in-pediatric-nephropathies
#20
Laura Penna Rocha, Samuel Cavalcante Xavier, Fernanda Rodrigues Helmo, Juliana Reis Machado, Fernando Silva Ramalho, Marlene Antônia Dos Reis, Rosana Rosa Miranda Corrêa
INTRODUCTION: Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells may express mesenchymal cell markers with subsequent change in their functions, and it may be part of the etiopathogenesis of kidney disease. OBJECTIVE: The aim of this study was to evaluate the immunexpression of some EMT inducers and markers in frequent nephropathies in pediatric patients. METHODS: 59 patients aged 2-18 years old were selected and divided into 6 groups of frequent nephropathies in children and adolescents, as well as one control group...
December 2016: Pathology, Research and Practice
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