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https://www.readbyqxmd.com/read/28106131/hif-1%C3%AE-induction-during-reperfusion-avoids-maladaptive-repair-after-renal-ischemia-reperfusion-involving-mir127-3p
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27693697/let-7d-mirna-prevents-tgf-%C3%AE-1-induced-emt-and-renal-fibrogenesis-through-regulation-of-hmga2-expression
#15
Ya Wang, Ying Le, Jun-Yu Xue, Zong-Ji Zheng, Yao-Ming Xue
TGF-β1-induced epithelial to mesenchymal transition (EMT) process of tubular epithelial cells plays a leading role in the occurrence and progression of renal fibrosis as seen in diabetic nephropathy (DN). High mobility group AT-hook 2 (HMGA2) is considered to be involved in TGF-β1-mediated EMT via multifactorial mechanisms. Specific microRNAs (miRNAs) are closely associated with EMT, and here we focused on let-7d miRNA as a regulator of HMGA2. This study aims to investigate the effects of HMGA2 on EMT process induced by TGF-β1 using small interfering RNA (siRNA) technique in vitro, and further explore the potential role of let-7d miRNA during renal fibrosis in DN...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27669116/diverse-functions-and-signal-transduction-of-the-exocyst-complex-in-tumor-cells
#16
REVIEW
Toshiaki Tanaka, Kaoru Goto, Mitsuyoshi Iino
The exocyst complex is a large conserved hetero-oligomeric complex that consists of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 subunits. It has been implicated in the targeting of vesicles for regulated exocytosis in various cell types, and is also important for targeted exocytosis of post-Golgi transport vesicles to the plasma membrane. The exocyst complex is essential for membrane growth, secretion, and function during exocytosis and endocytosis. Moreover, the individual components of the complex are thought to act on specific biological processes, such as cytokinesis, ciliogenesis, apoptosis, autophagy, and epithelial-mesenchymal transition (EMT)...
May 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27651308/efficacy-of-cotargeting-angiopoietin-2-and-the-vegf-pathway-in-the-adjuvant-postsurgical-setting-for-early-breast-colorectal-and-renal-cancers
#17
Florence T H Wu, Shan Man, Ping Xu, Annabelle Chow, Marta Paez-Ribes, Christina R Lee, Steven R Pirie-Shepherd, Urban Emmenegger, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKI) that target VEGF receptor-2 (VEGFR2) have not been effective as adjuvant treatments for micrometastatic disease in phase III clinical trials. Angiopoietin-2 (Ang2) is a proangiogenic and proinflammatory vascular destabilizer that cooperates with VEGF. The purpose of this study was to test whether CVX-060 (an Ang2-specific CovX-body) can be combined with VEGFR2-targeting TKIs (sunitinib or regorafenib) to successfully treat postsurgical metastatic disease in multiple orthotopically implanted human tumor xenograft and syngeneic murine tumor models...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27642944/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/27627216/nephroprotective-effects-of-metformin-in-diabetic-nephropathy
#19
REVIEW
Sreenithya Ravindran, Vinitha Kuruvilla, Kerry Wilbur, Shankar Munusamy
Metformin, a well-known anti-diabetic agent, is very effective in lowering blood glucose in patients with type 2 diabetes with minimal side-effects. Metformin is also being recommended in the treatment of obesity and polycystic ovary syndrome. Metformin elicits its therapeutic effects mainly via activation of AMP-activated kinase (AMPK) pathway. Renal cells under hyperglycemic or proteinuric conditions exhibit inactivation of cell defense mechanisms such as AMPK and autophagy, and activation of pathologic pathways such as mammalian target of rapamycin (mTOR), endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), oxidative stress, and hypoxia...
April 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27607429/alpha1-antitrypsin-attenuates-renal-fibrosis-by-inhibiting-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition
#20
Jang-Hee Cho, Hye-Myung Ryu, Eun-Joo Oh, Ju-Min Yook, Ji-Sun Ahn, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Yong-Lim Kim, Ihm Soo Kwak, Chan-Duck Kim
Alpha1-antitrypsin (AAT) exerts its anti-inflammatory effect through regulating the activity of serine proteinases. This study evaluated the inhibitory effects of AAT against the transforming growth factor (TGF)-β1 induced epithelial-to-mesenchymal transition (EMT) in unilateral ureter obstruction (UUO) mice and Madin-Darby canine kidney (MDCK) cells. C57BL/6 mice with induced UUO were injected intraperitoneally with AAT (80 mg/Kg) or vehicle for 7 days. MDCK cells were treated with TGF-β1 (2 ng/mL) for 48 hours to induce EMT, and co-treated with AAT (10 mg/mL) to inhibit the EMT...
2016: PloS One
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