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https://www.readbyqxmd.com/read/29234448/aristolochic-acid-induced-autophagy-promotes-epithelial-to-myofibroblast-transition-in-human-renal-proximal-tubule-epithelial-cells
#1
Yu-Lin Man, Hong-Liang Rui, Yi-Pu Chen, Guo-Qin Wang, Li-Jun Sun, Hong Cheng
Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29228653/overexpression-of-capn2-promotes-cell-metastasis-and-proliferation-via-akt-mtor-signaling-in-renal-cell-carcinoma
#2
Chenkui Miao, Chao Liang, Ye Tian, Aiming Xu, Jundong Zhu, Kai Zhao, Jianzhong Zhang, Yibo Hua, Shouyong Liu, Huiyu Dong, Chao Zhang, Shifeng Su, Pu Li, Chao Qin, Zengjun Wang
The calpain 2 (CAPN2) is upregulated in various malignant carcinomas. Previous studies have reported that CAPN2 functioned as an oncogenic factor in human cancers. However, its clinical role and potential effects on cell metastasis and proliferation in renal cell carcinoma (RCC) remain unknown. In this study, we evaluated the mRNA and protein levels of CAPN2 in human RCC specimens, matched normal specimens, and RCC cell lines using quantitative Real-time PCR (RT-PCR) and western blot. Immunohistochemistry of 74 RCC tissues in a tissue microarrays (TMAs) and normal kidney tissues were performed...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227974/mir302a-3p-may-modulate-renal-epithelial-mesenchymal-transition-in-diabetic-kidney-disease-by-targeting-zeb1
#3
Wen-Bin Tang, Linfeng Zheng, Renheng Yan, Jiayi Yang, Jianping Ning, Linlin Peng, Qiaoling Zhou, Liping Chen
BACKGROUND: Recent study found that microRNA (miRNA) are involved in diabetic kidney disease (DKD). The objective of this study is to determine the role of miR302a-3p in the process of renal epithelial-mesenchymal transition (EMT) in DKD. METHODS: The miRNA expression profiling of the cell line stimulated by high glucose was performed by a microarray analysis. Then real-time polymerase chain reaction (PCR) were used to determine the expression of one of the miRNAs significantly upregulated in cell line stimulated by high glucose, miR302a-3p...
December 8, 2017: Nephron
https://www.readbyqxmd.com/read/29221190/the-m6a-methyltransferase-mettl3-acting-as-a-tumor-suppressor-in-renal-cell-carcinoma
#4
Xiao Li, Jingyuan Tang, Wen Huang, Feng Wang, Pu Li, Chao Qin, Zhiqiang Qin, Qing Zou, Jifu Wei, Lixin Hua, Haiwei Yang, Zengjun Wang
We aimed to study the role of METTL3 in renal cell carcinoma (RCC) carcinogenesis and development. Immunohistochemistry was performed in clinical tissue microarray. Expression level of METTL3 in RCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. Then, the effects of METTL3 on proliferation, migration, invasion and cell cycle were studied in RCC cells. Additionally, in vivo study was carried out in nude mice. Negative METTL3 expression was associated with larger tumor size (P=0...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215709/the-potential-role-of-aquaporin-1-on-aristolochic-acid-i-induced-epithelial-mesenchymal-transition-on-hk-2-cells
#5
Ji Li, Mincheng Zhang, Yong Mao, Yimao Li, Xiaoxia Zhang, Xuehan Peng, Feng Yu
Aristolochic acid I (AA-I), one of the main active components in Aristolochaia herbs, may induce aristolochic acid nephropathy (AAN). Renal interstitial fibrosis is one of the most typical features of AAN. To investigate the mechanism of Aristolochic acid I (AA-I) -induced renal epithelial-mesenchymal transition (EMT) and determine the role of aquaporin-1 (AQP1) in this process, we established an AA-I-induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Morphological examination, MTT assay, and Western blot analysis were performed...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29209813/fsp1-specific-smad2-knockout-in-renal-tubular-endothelial-and-interstitial-cells-reduces-fibrosis-and-epithelial-to-mesenchymal-transition-in-murine-stz-induced-diabetic-nephropathy
#6
Ivonne Loeffler, Marita Liebisch, Stefanie Allert, Elke Kunisch, Raimund W Kinne, Gunter Wolf
Extracellular matrix deposition during tubulointerstitial fibrosis (TIF), a central pathological process in patients with diabetic nephropathy (DN), is driven by locally activated, disease-relevant myofibroblasts. Myofibroblasts can arise from various cellular sources, e.g., tubular epithelial cells via a process named epithelial-to-mesenchymal transition (EMT). Transforming growth factor beta 1 (TGF-β1) and its downstream Smad signaling play a critical role in both TIF and EMT. Whereas Smad3 is one central mediator, the role of the other prominently expressed variant, Smad2, is not completely understood...
December 6, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29204790/cytoplasmic-expression-of-twist1-an-emt-related-transcription-factor-is-associated-with-higher-grades-renal-cell-carcinomas-and-worse-progression-free-survival-in-clear-cell-renal-cell-carcinoma
#7
Arezoo Rasti, Zahra Madjd, Maryam Abolhasani, Mitra Mehrazma, Leila Janani, Leili Saeednejad Zanjani, Mojgan Asgari
Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial-mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical significance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defined renal tumor tissues, including 173 (68.7%) clear cell renal cell carcinomas (ccRCC), 45 (17...
December 4, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29198924/sinomenine-hydrochloride-attenuates-the-proliferation-migration-invasiveness-angiogenesis-and-epithelial-mesenchymal-transition-of-clear-cell-renal-cell-carcinoma-cells-via-targeting-smad-in-vitro
#8
Bin Zhao, Lei Liu, Jun Mao, Kun Liu, Weiwang Fan, Jiheng Liu, Zhiwei Zhang, Quanlin Li
New strategies for the treatment of clear-cell renal cell carcinoma (ccRCC) are urgently needed. Recently, accumulating evidence has demonstrated that sinomenine hydrochloride (SH), extracted from the plant sinomenium acutum, has potent anti-cancer activity in multiple human malignant solid tumors. However, the underlying molecular mechanism by which SH treatment exerts its antagonizing tumorigenic effects has not been clearly elucidated. In this study, we showed that SH treatment exerted profound effects on cell growth in ccRCC in a dose- and time-dependent manner in vitro...
November 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29194709/low-grade-spindle-cell-proliferation-in-clear-cell-renal-cell-carcinoma-is-unlikely-to-be-an-initial-step-in-sarcomatoid-differentiation
#9
Ozlem Tanas Isikci, Huying He, Petr Grossmann, Reza Alaghehbandan, Monika Ulamec, Kvetoslava Michalova, Kristyna Pivovarcikova, Delia Perez Montiel, Ondrej Ondic, Ondrej Daum, Kristyna Prochazkova, Milan Hora, Michal Michal, Ondrej Hes
Spindle cell proliferation within clear cell renal cell carcinoma (ccRCC) is usually considered as sarcomatoid differentiation. Low-grade spindle cell proliferation (LG-SCP) in ccRCC was first described in 2001. This phenomenon is not common and can pose diagnostic challenges particularly in core biopsies. The aim of this study was to describe morphologic, immunohistochemical and molecular characteristics of ccRCCs with LG-SCP. 11 cases of ccRCC with LG-SCP were retrieved from approximately 21,000 renal tumors in our registry...
December 1, 2017: Histopathology
https://www.readbyqxmd.com/read/29193729/fhl2-promotes-tubular-epithelial-to-mesenchymal-transition-through-modulating-%C3%AE-catenin-signalling
#10
Ting Cai, Danqin Sun, Ying Duan, Yumei Qiu, Chunsun Dai, Junwei Yang, Weichun He
β-Catenin signalling plays an important role in regulating tubular epithelial-to-mesenchymal transition (EMT), an indispensable programme for driving renal fibrosis. As an adapter protein, four and a half LIM domain protein 2 (FHL2) acts as a coregulator of β-catenin in several other cell types. To determine whether FHL2 affects β-catenin signalling and thus is involved in tubular EMT, we examined its expression and function in the process of TGF-β1-induced EMT. FHL2 mRNA and protein were induced by TGF-β1 in rat tubular epithelial cells (NRK-52E), an effect that intracellular Smad signalling was required...
November 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29174387/role-of-tumor-necrosis-factor-%C3%AE-in-epithelial-to-mesenchymal-transition-in-transplanted-kidney-cells-in-recipients-with-chronic-allograft-dysfunction
#11
Chunchun Zhao, Zhen Xu, Zijie Wang, Chuanjian Suo, Jun Tao, Zhijian Han, Min Gu, Ruoyun Tan
BACKGROUND: Chronic allograft dysfunction (CAD) is characterized by allograft kidney interstitial fibrosis, the underlying mechanism of which is unclear. Our aim was to elucidate the role and mechanism of TNF-α-induced epithelial-to-mesenchymal transition (EMT) in transplant kidney tubular interstitial fibrosis. METHODS: Human kidney tissues from normal volunteers and CAD patients were assessed using periodic acid-Schiff, Masson trichrome and immunohistochemical staining...
November 23, 2017: Gene
https://www.readbyqxmd.com/read/29170782/coordination-driven-assembly-of-catechol-modified-chitosan-for-the-kidney-specific-delivery-of-salvianolic-acid-b-to-treat-renal-fibrosis
#12
Jing Li, Cuiting Zhang, Weiming He, Hongzhi Qiao, Jiahui Chen, KaiKai Wang, David Oupický, Minjie Sun
Kidney-specific delivery is critically important for the treatment of renal fibrosis with drugs such as salvianolic acid B (Sal B). Here we report a kidney-specific nanocomplex formed by the coordination-driven assembly of catechol-modified low molecular weight chitosan (HCA-Chi), calcium ions and Sal B. The prepared HCA-Chi-Ca-Sal B (HChi-Ca-Sal B) nanocomplex reversed the TGF-β1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells. In vivo imaging demonstrated a kidney-specific biodistribution of the nanocomplex...
November 24, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29163166/saxagliptin-attenuates-albuminuria-by-inhibiting-podocyte-epithelial-to-mesenchymal-transition-via-sdf-1%C3%AE-in-diabetic-nephropathy
#13
Yun-Peng Chang, Bei Sun, Zhe Han, Fei Han, Shao-Lan Hu, Xiao-Yu Li, Mei Xue, Yang Yang, Li Chen, Chun-Jun Li, Li-Ming Chen
The dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin has been found to reduce progressive albuminuria, but the exact mechanism of inhibition is unclear. Podocyte epithelial-to-mesenchymal transition (EMT) has emerged as a potential pathway leading to proteinuria in diabetic nephropathy (DN). Stromal cell-derived factor-1α (SDF-1α), one of the substrates of DPP-4, can activate the protein kinase A pathway and subsequently inhibit its downstream effector, transforming growth factor-β1 (TGF-β1), which induces podocyte EMT...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29160908/connective-tissue-growth-factor-induces-renal-fibrosis-via-epidermal-growth-factor-receptor-activation
#14
Sandra Rayego-Mateos, José Luis Morgado-Pascual, Raúl R Rodrigues-Diez, Raquel Rodrigues-Diez, Lucas Falke, Sergio Mezzano, Alberto Ortiz, Jesús Egido, Roel Goldschmeding, Marta Ruiz-Ortega
Connective tissue growth factor (CCN2/CTGF) is a matricellular protein overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates production of extracellular matrix (ECM) proteins and epithelial mesenchymal transition (EMT), and therefore could contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have described that CCN2 and its C-terminal degradation product CCN2(IV), bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29158549/hypoxia-inducible-factor-1%C3%AE-mediates-the-profibrotic-effect-of-albumin-in-renal-tubular-cells
#15
Junping Hu, Weili Wang, Fan Zhang, Pin-Lan Li, Krishna M Boini, Fan Yi, Ningjun Li
Proteinuria is closely associated with the progression of chronic kidney diseases (CKD) by producing renal tubulointerstitial fibrosis. Over-activation of hypoxia inducible factor (HIF)-1α has been implicated in the progression of CKD. The present study tested the hypothesis that HIF-1α mediates albumin-induced profibrotic effect in cultured renal proximal tubular cells. Incubation of the cells with albumin (40 μg/ml) for 72 hrs significantly increased the protein levels of HIF-1α, tissue inhibitor of metalloproteinase (TIMP)-1 and collagen-I, which were blocked by HIF-1α shRNA...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157821/poricoic-acid-za-a-novel-ras-inhibitor-attenuates-tubulo-interstitial-fibrosis-and-podocyte-injury-by-inhibiting-tgf-%C3%AE-smad-signaling-pathway
#16
Ming Wang, Dan-Qian Chen, Min-Chang Wang, Hua Chen, Lin Chen, Dan Liu, Hui Zhao, Ying-Yong Zhao
BACKGROUND: The pathogenesis of tubulo-interstitial fibrosis and glomerulosclerosisis was characterized by cellular hypertrophy, extracellular matrix accumulation and podocyte detachment. Poricoic acid ZA (PZA) is a tetracyclic triterpenoid compound extracted from the surface layer of Poria cocos (LPC), which have been used extensively for diuretic and renoprotective effects. METHODS: The anti-fibrotic effect of PZA is investigated in HK-2 cells and podocytes induced by TGF-β1 and angiotensin II (ANGII)...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29150436/microvesicles-derived-from-human-wharton-s-jellymesenchymal-stem-cells-ameliorate-ischemia-reperfusion-induced-renal-fibrosis-by-releasing-from-g2-m-cell-cycle-arrest
#17
Wenxia Chen, Yongbin Yan, Chundong Song, Ying Ding, Tao Du
Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI), however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator HGF or inhibitor U0126 was administrated, respectively. Tubular cell proliferation and apoptosis were identified by Ki67 or TUNEL immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin (α -SMA) staining were used for assessing renal fibrosis...
November 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#18
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29138866/hmga2-facilitates-epithelial-mesenchymal-transition-in-renal-cell-carcinoma-by-regulating-the-tgf-%C3%AE-smad2-signaling-pathway
#19
Bo Kou, Wei Liu, Xiaoshuang Tang, Qingshan Kou
High-mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, has been reported to correlate with cancer progression. However, there is no report concerning the correlation between HMGA2 and metastasis in renal cell carcinoma. In the present study, we found that HMGA2 was highly expressed in five renal cell carcinoma cell lines compared with that in the normal renal tubular epithelial HK2 cell line. Additionally, HMGA2 facilitated cell migration and invasion of renal cell carcinoma cells, as evidenced by wound healing and Transwell assays...
November 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29128370/the-inhibition-of-sphingomyelin-synthase-1-activity-induces-collecting-duct-cells-to-lose-their-epithelial-phenotype
#20
Yamila Romina Brandán, Edith Del Valle Guaytima, Nicolás Octavio Favale, Lucila Gisele Pescio, Norma B Sterin-Speziale, María Gabriela Márquez
Epithelial tissue requires that cells attach to each other and to the extracellular matrix by the assembly of adherens junctions (AJ) and focal adhesions (FA) respectively. We have previously shown that, in renal papillary collecting duct (CD) cells, both AJ and FA are located in sphingomyelin (SM)-enriched plasma membrane microdomains. In the present work, we investigated the involvement of SM metabolism in the preservation of the epithelial cell phenotype and tissue organization. To this end, primary cultures of renal papillary CD cells were performed...
November 8, 2017: Biochimica et Biophysica Acta
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