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https://www.readbyqxmd.com/read/29029361/the-mechanism-of-attenuation-of-epithelial-mesenchymal-transition-by-a-phosphodiesterase-5-inhibitor-via-renal-klotho-expression
#1
Seung Tae Han, Jae Seok Kim, Jun Young Lee, Min Keun Kim, Jin Sae Yoo, Byoung Geun Han, Seung Ok Choi, Jae Won Yang
OBJECTIVES: Phosphodiesterase-5 (PDE-5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the down-regulation of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE-5 inhibitor could preserve epithelial mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression...
October 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29021386/suppression-of-microrna-activity-in-kidney-collecting-ducts-induces-partial-loss-of-epithelial-phenotype-and-renal-fibrosis
#2
Sachin Hajarnis, Matanel Yheskel, Darren Williams, Thomas Brefort, Bob Glaudemans, Huguette Debaix, Michel Baum, Olivier Devuyst, Vishal Patel
microRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. The physiologic function of these noncoding RNAs in postnatal renal tubules still remains unclear. Surprisingly, they appear to be dispensable for mammalian proximal tubule (PT) function. Here, we examined the effects of miRNA suppression in collecting ducts (CDs). To conclusively evaluate the role of miRNAs, we generated three mouse models with CD-specific inactivation of key miRNA pathway genes Dicer, Dgcr8, and the entire Argonaute gene family (Ago1, 2, 3, and 4)...
October 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29017152/high-uric-acid-induced-epithelial-mesenchymal-transition-of-renal-tubular-epithelial-cells-via-the-tlr4-nf-kb-signaling-pathway
#3
Huifang Liu, Jiachuan Xiong, Ting He, Tangli Xiao, Yan Li, Yanlin Yu, Yinghui Huang, Xinli Xu, Yunjian Huang, Jingbo Zhang, Bo Zhang, Jinghong Zhao
BACKGROUND: Hyperuricemia is an independent risk factor for causing chronic kidney disease and contributes to kidney fibrosis. After urate crystals get deposited in the kidney, they can cause hyperuricemia nephropathy, leading to glomerular hypertrophy and renal tubular interstitial fibrosis. Recent data showed that uric acid (UA) could induce epithelial mesenchymal transition (EMT) of renal tubular cells, in which NRLP3 inflammatory pathway was involved. However, whether TLR4/NF-κB signaling pathway is also involved in EMT of renal tubular cells induced by UA is not clear...
October 10, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28991230/alu-rna-accumulation-induces-epithelial-to-mesenchymal-transition-by-modulating-mir-566-and-is-associated-with-cancer-progression
#4
F Di Ruocco, V Basso, M Rivoire, P Mehlen, J Ambati, S De Falco, V Tarallo
Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28990102/role-of-artesunate-in-tgf%C3%A2-%C3%AE-1%C3%A2-induced-renal-tubular-epithelial%C3%A2-mesenchymal-transdifferentiation-in-nrk%C3%A2-52e-cells
#5
Yaqian Zhang, Huanhuan Li, Jiajun Zhu, Tiantian Wei, Yingxian Peng, Ran Li, Rui Xu, Mei Li, Anzhou Xia
The implications of epithelial‑mesenchymal transdifferentiation (EMT) have extended beyond the confines of renal fibrosis to renal tubulointerstitial fibrosis. It has been proposed that EMT may be one of the mechanisms involved in the pathogenesis of renal fibrosis. However, the underlying mechanisms remain unknown. Transforming growth factor (TGF)‑β1 is considered to be an important cytokine which regulates the transdifferentiation of tubular epithelial cells into myofibroblasts in renal tubulointerstitial fibrosis...
October 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28983605/ldha-promotes-tumor-metastasis-by-facilitating-epithelial%C3%A2-mesenchymal-transition-in-renal-cell-carcinoma
#6
Juping Zhao, Xin Huang, Zhaoping Xu, Jun Dai, Hongchao He, Yu Zhu, Haofei Wang
Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay...
September 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28973641/l-carnitine-via-ppar%C3%AE-and-sirt1-dependent-mechanisms-attenuates-epithelial-mesenchymal-transition-and-renal-fibrosis-caused-by-perfluorooctanesulfonate
#7
Hsiu-Chu Chou, Li-Li Wen, Chih-Cheng Chang, Chien-Yu Lin, Lu Jin, Shu-Hui Juan
We have previously reported that perfluorooctanesulfonate (PFOS) causes cell apoptosis in renal tubular epithelial cells (RTCs). Here, we extend our findings and provide evidence of epithelial-mesenchymal transition (EMT)-associated renal fibrosis caused by PFOS and the protection by L-carnitine. Our results demonstrate that PFOS increased the expression of EMT and renal injury biomarkers (e.g., N-cadherin, vimentin, Snail, Kim1, and Lcn2). Additionally, PFOS caused EMT induction through Sirt1-mediated PPARγ deacetylation and inactivation...
August 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28921581/mir-122-promotes-metastasis-of-clear-cell-renal-cell-carcinoma-by-downregulating-dicer
#8
Yang Fan, Xin Ma, Hongzhao Li, Yu Gao, Qingbo Huang, Yu Zhang, Xu Bao, Qingshan Du, Guoxiong Luo, Kan Liu, Qingyu Meng, Chaofei Zhao, Xu Zhang
Although overall downregulation of microRNAs (miRNAs) is a general feature of clear-cell renal cell carcinoma (ccRCC), several miRNAs are consistently upregulated, among which miR-122 was markedly increased in ccRCC tissues. This study aims to determine the functional importance and underlying mechanism of miR-122 in ccRCC metastasis. Here we demonstrate that the expression of miR-122 increased in ccRCC tissues, and higher miR-122 expression was found in ccRCC tissues with metastatic disease than in those without metastasis...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28901475/valproic-acid-inhibits-epithelial%C3%A2-mesenchymal-transition-in-renal-cell-carcinoma-by-decreasing-smad4-expression
#9
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/28877670/indoleamine-2-3-dioxygenase-ido-increases-during-renal-fibrogenesis-and-its-inhibition-potentiates-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition
#10
Luiz Henrique Gomes Matheus, Gislene Mendes Simão, Taíssa Altieri Amaral, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Yves Silva Teles Matos, Alexandre Chagas Santana, Gabriela Gomes Cardoso Rodrigues, Maria Clara Albejante, Erna Elisabeth Bach, Maria Aparecida Dalboni, Cleber Pinto Camacho, Humberto Dellê
BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is an immunomodulatory molecule that has been implicated in several biological processes. Although IDO has been linked with some renal diseases, its role in renal fibrosis is still unclear. Because IDO may be modulated by TGF-β1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-β1-induced tubular epithelial-mesenchymal transition (EMT). We analyzed the IDO expression and activity in a model of renal fibrogenesis, and the effect of the IDO inhibitor 1-methyl-tryptophan (MT) on TGF-β1-induced EMT using tubular cell culture...
September 6, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28861152/microrna-138-attenuates-epithelial-to-mesenchymal-transition-by-targeting-sox4-in-clear-cell-renal-cell-carcinoma
#11
Feng Liu, Linfeng Wu, Anping Wang, Yajun Xu, Xiaodong Luo, Xing Liu, Yi Hua, Deying Zhang, Shengde Wu, Tao Lin, Dawei He, Guanghui Wei, Shanwen Chen
MicroRNAs (miRNAs) are small, non-coding RNAs which can serve as oncogenes or tumor suppressor genes in human cancers. Herein, the transcriptomic differences of miRNAs in ccRCC were globally assessed using publicly available microarray dataset (GSE71302) from Gene Expression Omnibus (GEO) and we identified miR-138 as a potential onco-suppressive miRNA. We further found that the expression of miR-138 was dramatically decreased in ccRCC cell lines and clinical ccRCC tissue samples, and the low miR-138 expression was closely correlated with tumor progression and prognosis in ccRCC patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28859984/epstein-barr-virus-encoded-latent-membrane-protein-1-induces-epithelial-to-mesenchymal-transition-by-inducing-v-set-ig-domain-containing-4-vsig4-expression-via-nf-kb-in-renal-tubular-epithelial-hk-2%C3%A2-cells
#12
Seung-Mi Kim, Se Won Oh, Sang Hyun Park, Dae Young Hur, Seung-Woo Hong, Sang Youb Han
The epithelial to mesenchymal transition (EMT), a hallmark of chronic kidney disease, is a key event in the conversion from tubular epithelial cells to myofibroblasts in renal fibrosis. Epstein-Barr virus (EBV) is a γ-herpes oncovirus associated with chronic kidney disease. However, the relationship between EBV and the EMT process in renal tubular epithelial cells is not well understood. Among EBV-latent genes, EBV-encoded latent membrane protein 1 (LMP1) induces EMT by regulating a variety of molecules in EBV-induced oncogenic transformation...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28858976/galectin-3-pharmacological-inhibition-attenuates-early-renal-damage-in-spontaneously-hypertensive-rats
#13
Ernesto Martínez-Martínez, Jaime Ibarrola, Amaya Fernández-Celis, Laurent Calvier, Celine Leroy, Victoria Cachofeiro, Patrick Rossignol, Natalia López-Andrés
BACKGROUND: The pharmacological blockade of galectin-3 (Gal-3), a β-galactoside-binding lectin, reduces renal impairment in acute kidney injury, hyperaldosteronism or nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in renal damage in spontaneously hypertensive rats (SHRs). METHODS AND RESULTS: Gal-3 inhibition did not modify blood pressure levels in 30-week-old SHR. Kidney weight was higher in SHR, with no effect of MCP treatment (100 mg/kg/day in the drinking water)...
August 30, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28846080/growth-induced-stress-enhances-epithelial-mesenchymal-transition-induced-by-il-6-in-clear-cell-renal-cell-carcinoma-via-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway
#14
Q Chen, D Yang, H Zong, L Zhu, L Wang, X Wang, X Zhu, X Song, J Wang
Stromal cell populations in the tumor microenvironment (TME) play a critical role in the oncogenesis and metastasis of renal cell carcinoma. In this study, we found that there are α-smooth muscle actin positive (α-SMA (+)) cells in the stroma of clear cell renal cell carcinoma (ccRCC) tissues, and their numbers are significantly associated with poor survival in ccRCC patients. Interleukin 6 (IL-6) is a critical diver that induces α-SMA (+) cells in ccRCC tissues via promotion of epithelial to mesenchymal transition (EMT) and stimulates migration and invasion in ccRCC...
August 28, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28839221/exosomes-from-high-glucose-treated-glomerular-endothelial-cells-trigger-the-epithelial-mesenchymal-transition-and-dysfunction-of-podocytes
#15
Xiaoming Wu, Yanbin Gao, Liping Xu, Wanyu Dang, Huimin Yan, Dawei Zou, Zhiyao Zhu, Liangtao Luo, Nianxiu Tian, Xiaolei Wang, Yu Tong, Zheji Han
New data indicate that abnormal glomerular endothelial cell (GEC)-podocyte crosstalk plays a critical role in diabetic nephropathy (DN). The aim of our study is to investigate the role of exosomes from high glucose (HG)-treated GECs in the epithelial-mesenchymal transition (EMT) and dysfunction of podocytes. In this study, exosomes were extracted from GEC culture supernatants and podocytes were incubated with the GEC-derived exosomes. Here, we demonstrate that HG induces the endothelial-mesenchymal transition (EndoMT) of GECs and HG-treated cells undergoing the EndoMT secrete more exosomes than normal glucose (NG)-treated GECs...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817830/microrna-200a-inhibits-transforming-growth-factor-%C3%AE-1-induced-proximal-tubular-epithelial-mesenchymal-transition-by-targeting-%C3%AE-catenin
#16
Yi Gong, Zhexue Qin, Baoshang Zhou, Hua Chen, Zhengmin Shi, Jing Zhang
BACKGROUND: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin...
August 18, 2017: Nephron
https://www.readbyqxmd.com/read/28802251/microrna-720-regulates-e-cadherin-%C3%AE-e-catenin-complex-and-promotes-renal-cell-carcinoma
#17
Nadeem S Bhat, Melissa Colden, Altaf A Dar, Sharanjot Saini, Prerna Arora, Varahram Shahryari, Soichiro Yamamura, Yuichiro Tanaka, Taku Kato, Shahana Majid, Rajvir Dahiya
MicroRNAs are implicated in regulating cancer progression and metastasis. Here we show that miR-720 is positively associated with renal cell carcinoma (RCC). Elevated levels of miR-720 were observed in a panel of RCC cell lines and clinical tissues compared to non-malignant cell line and normal samples. Loss of miR-720 function inhibited proliferation, migration and invasion and induced apoptosis in RCC cell lines in vitro and repressed tumor growth in xenograft mouse model. Conversely, gain of miR-720 function in non-malignant HK-2 cells induced pro-cancerous characteristics...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#18
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28790310/p16-ink4a-deletion-ameliorated-renal-tubulointerstitial-injury-in-a-stress-induced-premature-senescence-model-of-bmi-1-deficiency
#19
Jianliang Jin, Jianguo Tao, Xin Gu, Zhenzhen Yu, Rong Wang, Guoping Zuo, Qing Li, Xianhui Lv, Dengshun Miao
To determine whether p16 (INK4a) deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1 (-/-)) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16 (INK4a) double-knockout, and Bmi-1 (-/-) and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28772211/autophagy-as-a-potential-therapeutic-target-during-epithelial-to-mesenchymal-transition-in-renal-cell-carcinoma-an-in-vitro-study
#20
Mamta Singla, Shalmoli Bhattacharyya
Cancer progression toward invasive and metastatic disease is aided by reactivation of epithelial-mesenchymal transition (EMT), involving transdifferentiation of epithelial cells into mesenchymal phenotype. This leads to increased migratory and stem cell-like features in the cells. These EMT cells are more resistant to chemotherapy and it is hypothesized that the phenomenon of autophagy induces resistance, providing a survival strategy for cells. In the present study, we induced EMT-like phenotype in renal carcinoma cells and identified corresponding higher autophagy flux in these cells...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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