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Kidney epithelial to mesenchymal transition

Ling Hou, Yue Du, Chengguang Zhao, Yubin Wu
PURPOSE: We sought to investigate the role of PAX2 in renal epithelial-to-mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10 expression during renal EMT and ADAM10 expression in fibrotic kidneys. METHODS: A rat renal tubular epithelial cell line, NRK52E, was transfected with lentivirus carrying PAX2, and E-cadherin and α-SMA expressions were measured. The influence of PAX2 on ADAM10 promoter activity was evaluated using chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assay...
August 16, 2018: International Urology and Nephrology
Yu-Kun Li, Yuan-Jie Xie, Dai-Chao Wu, Shuang-Lian Long, Shengsong Tang, Zhong-Cheng Mo
The novel neurite outgrowth inhibitor B (Nogo‑B) receptor (NgBR) is specific for Nogo‑B, which is highly expressed in various human organs and cells, including the lung, liver, kidney, smooth muscle cells, blood vessel endothelial cells and inflammatory cells. Previous studies have indicated that NgBR directly interacts with Nogo‑B and is able to independently influence lipid and cholesterol homeostasis, angiogenesis, N‑glycosylation, the epithelial-mesenchymal transition, the chemotaxis of endothelial cells and cellular proliferation and apoptosis...
August 9, 2018: International Journal of Oncology
Siu Chiu Chan, Ying Zhang, Annie Shao, Svetlana Avdulov, Jeremy Herrera, Karam Aboudehen, Marco Pontoglio, Peter Igarashi
BACKGROUND: Mutation of HNF1B , the gene encoding transcription factor HNF-1 β , is one cause of autosomal dominant tubulointerstitial kidney disease, a syndrome characterized by tubular cysts, renal fibrosis, and progressive decline in renal function. HNF-1 β has also been implicated in epithelial-mesenchymal transition (EMT) pathways, and sustained EMT is associated with tissue fibrosis. The mechanism whereby mutated HNF1B leads to tubulointerstitial fibrosis is not known. METHODS: To explore the mechanism of fibrosis, we created HNF-1 β -deficient mIMCD3 renal epithelial cells, used RNA-sequencing analysis to reveal differentially expressed genes in wild-type and HNF-1 β -deficient mIMCD3 cells, and performed cell lineage analysis in HNF-1 β mutant mice...
August 10, 2018: Journal of the American Society of Nephrology: JASN
Girish Talakatta, Mohsen Sarikhani, Jaseer Muhamed, K Dhanya, Bagganahalli S Somashekar, Padukudru Anand Mahesh, Nagalingam Sundaresan, P V Ravindra
In the long term, diabetes profoundly affects multiple organs, such as the kidney, heart, brain, liver, and eyes. The gradual loss of function in these vital organs contributes to mortality. Nonetheless, the effects of diabetes on the lung tissue are not well understood. Clinical and experimental data from our studies revealed that diabetes induces inflammatory and fibrotic changes in the lung. These changes were mediated by TGF-β-activated epithelial-to-mesenchymal transition (EMT) signaling pathways. Our studies also found that glucose restriction promoted mesenchymal-to-epithelial transition (MET) and substantially reversed inflammatory and fibrotic changes, suggesting that diabetes-induced EMT was mediated in part by the effects of hyperglycemia...
August 9, 2018: Scientific Reports
Carolline Fernanda Rodrigues Ascenção, Raghavendra Sashi Krishna Nagampalli, Zeyaul Islam, Matheus Pinto Pinheiro, Larissa Menezes Dos Reis, Bianca Alves Pauletti, Carolina Aparecida de Guzzi Cassago, Daniela Campos Granato, Adriana Franco Paes Leme, Sandra Martha Gomes Dias
The mitochondrial phosphate-activated glutaminase C (GAC) is produced by the alternative splicing of the GLS gene. Compared to the other GLS isoform, the kidney-type glutaminase (KGA), GAC is more enzymatically efficient and of particular importance for cancer cell growth. Although its catalytic mechanism is well understood, little is known about how post-translational modifications can impact GAC function. Here, we identified by mass spectrometry a phosphorylated serine at the GLS N-terminal domain (at position 95) and investigated its role on regulating GAC activity...
August 6, 2018: Biochimie
Weiwei Xi, Xuming Zhao, Meijun Wu, Wenjuan Jia, Hua Li
Although microRNA-155 (miR-155) is implicated in the pathogenesis of several fibrotic diseases, information regarding its functional role in renal fibrosis is limited. The current study aims to investigate the effects of miR-155 on renal fibrosis in unilateral ureteral occlusion (UUO) mice. MiR-155 level was significantly increased in renal tissues of UUO mice and TGF-β1-treated HK2 cells. Masson's trichrome staining showed that delivery of adeno-associated virus encoding miR-155 inhibitor led to a decrease in renal fibrosis induced by UUO...
August 6, 2018: Cell Biology International
Eva Gravesen, Anders Nordholm, Maria Mace, Marya Morevati, Estrid Høgdall, Carsten Nielsen, Andreas Kjær, Klaus Olgaard, Ewa Lewin
Uremic vascular calcification is a regulated cell-mediated process wherein cells in the arterial wall transdifferentiate to actively calcifying cells resulting in a process resembling bone formation. Wnt signalling is established as a major driver for vessel formation and maturation and for embryonic bone formation, and disturbed Wnt signalling might play a role in vascular calcification. ICG-001 is a small molecule Wnt inhibitor that specifically targets the coactivator CREB binding protein (CBP)/β-catenin-mediated signalling...
2018: PloS One
Haisam Shah, Alison Hacker
No abstract text is available yet for this article.
July 30, 2018: Journal of Physiology
Katharina Schütte-Nütgen, Maria Edeling, Gudrun Mendl, Michael P Krahn, Bayram Edemir, Thomas Weide, Joachim Kremerskothen, Ulf Michgehl, Hermann Pavenstädt
Reactivation of Notch signaling in kidneys of animal models and patients with chronic kidney disease (CKD) has been shown to contribute to epithelial injury and fibrosis development. Here, we investigated the mechanisms of Notch-induced injury in renal epithelial cells. We performed genome-wide transcriptome analysis to identify Notch target genes using an in vitro system of cultured tubular epithelial cells expressing the intracellular domain of Notch1. One of the top downregulated genes was Disabled-2 ( Dab2)...
July 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Nianxiu Tian, Yanbin Gao, Xiaolei Wang, Xiaoming Wu, Dawei Zou, Zhiyao Zhu, ZheJi Han, Tao Wang, Yimin Shi
Background: Endoplasmic reticulum stress is associated with podocyte apoptosis in the pathogenesis of diabetic nephropathy (DN). A previous study has demonstrated that emodin has a protective effect in the kidney by suppressing proliferation of mesangial cells and inhibiting the renal tubular epithelial-to-mesenchymal transition. However, the effects of emodin on the podocyte apoptosis in DN and its mechanisms are unknown. Aim: This study aimed to explore the effect of emodin on DN model KK-Ay mice and high glucose induced podocytes apoptosis via the PERK-eIF2α pathway...
2018: Drug Design, Development and Therapy
Roberto Campagna, Monia Cecati, Valentina Pozzi, Stefania Fumarola, Veronica Pompei, Giulio Milanese, Andrea Benedetto Galosi, Davide Sartini, Monica Emanuelli
Renal cell carcinoma (RCC) is the most common tumor of the kidney and its major histologic subtype is clear cell RCC (ccRCC). About 30% of diagnosed ccRCCs already have metastasis. Traditionally, localized ccRCC is treated with nephrectomy but the relapse rate is 30%. Thus, the discovery of effective biomarkers for early detection, as well as the identification of new targets for molecular-based therapy of ccRCC are urgently required. In this study, we focused on molecules that could modulate the trascription of the enzyme nicotinamide N-methyltransferase (NNMT) that is known to be up-regulated in ccRCC...
May 30, 2018: Cellular and Molecular Biology
Lu Wang, Yu Fan, Lian Zhang, Lili Li, Guanyu Kuang, Cheng Luo, Chen Li, Tingxiu Xiang, Qian Tao, Qian Zhang, Jianming Ying
SOX7 (SRY-related high mobility group box 7), a high mobility group protein, is reported to be down-regulated in several cancer types, which indicates an important role in tumorigenesis; however, its biologic role in renal cell carcinoma (RCC) pathogenesis remains unknown. We studied the alterations and functions of SOX7 in RCC. We detected its broad expression in multiple human normal tissues, including kidney, but frequent down-regulation in RCC cell lines and primary tumors. Promoter CpG methylation seems to directly mediate SOX7 silencing in RCC cells, which could be reversed by demethylation treatment...
June 29, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Lei Liu, Yiping Li, Zhi Wang, Fengan Ding, Zhengyuan Cheng, Qing Xu, Yingying Cai, Manoj Hang Limbu, Yiqiong Yang, Bicheng Liu, Pingsheng Chen
Most patients with chronic kidney disease (CKD) present with proteinuria and extracellular matrix (ECM) deposition in the interstitium. Matrix metalloproteinase-2 (MMP-2) is important for maintaining ECM metabolism and it affects the formation and development of CKD. Autophagy has been reported to be protective against renal tubular injury, but the role of autophagy related to ECM metabolism is unclear. Rab7 is a shared molecule of endocytosis and autophagy. The aim of this study is to explore the role of autophagy in regulating MMP-2 activity and to determine whether Rab7 functions in regulating MMP-2 activity and injury in albumin-overloaded TECs...
June 19, 2018: Experimental Cell Research
Gagandeep Kaur, Caiyun Grace Li, Andrew Chantry, Cherie Stayner, Julia Horsfield, Michael R Eccles
Canonical TGF-β1 signalling promotes tumor progression by facilitating invasion and metastasis, whereby release of TGF-β1, by (for example) infiltrating immune cells, induces epithelial to mesenchymal transition (EMT). PAX2, a member of the Paired box family of transcriptional regulators, is normally expressed during embryonic development, including in the kidney, where it promotes mesenchymal to epithelial transition (MET). PAX2 expression is silenced in many normal adult tissues. However, in contrast, PAX2 is expressed in several cancer types, including kidney, prostate, breast, and ovarian cancer...
June 1, 2018: Oncotarget
Weina Wang, Aimei Wang, Guochang Luo, Fengqiao Ma, Xiaoming Wei, Yongyi Bi
Ischemia/reperfusion (I/R) is a major cause of acute kidney injury (AKI), along with delayed graft function, which can trigger chronic kidney injury by stimulating epithelial to mesenchymal transition (EMT) in the kidney canaliculus. Sphingosine 1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is indispensable for vessel homeostasis. This study aimed to investigate the influence of S1P1 on the mechanisms underlying I/R-induced EMT in the kidney using in vivo and in vitro models. Wild-type (WT) and S1P1-overexpressing kidney canaliculus cells were subject to hypoxic conditions followed by reoxygenation in the presence or absence of FTY720-P, a potent S1P1 agonist...
July 1, 2018: Acta Biochimica et Biophysica Sinica
Jin Sug Kim, Gi-Ja Lee, Tae Won Lee, Chun Gyoo Ihm, Yu Ho Lee, Yang Gyun Kim, Ju-Young Moon, Sang Ho Lee, Ji-Hye Kim, Sung-Wook Kang, Su-Jin Chae, Hun-Kuk Park, Kyung Hwan Jeong
Objective: Angiotensin II (Ang II) plays a profibrotic role in the kidneys. Although many pathways of Ang II have been discovered, the morphological and mechanical aspects have not been well investigated. We observed the changes in tubular epithelial cells (TECs) after Ang II treatment with or without Ang II receptor blockers (ARBs) using atomic force microscopy (AFM). Methods: TECs were stimulated with Ang II with or without telmisartan, PD123319, and blebbistatin...
2018: BioMed Research International
Katsue Suzuki-Inoue
Podoplanin is a type-I transmembrane sialomucin-like glycoprotein expressed on the surface of several kinds of tumor cells. The podoplanin receptor is a platelet activation receptor known as C-type lectin-like receptor 2 (CLEC-2), which has been identified as a receptor for the platelet-activating snake venom protein rhodocytin. CLEC-2 is highly expressed in platelets and megakaryocytes and expressed at lower levels in liver Kupffer cells. Podoplanin is expressed in certain types of tumor cells, including squamous cell carcinomas, seminomas, and brain tumors...
June 4, 2018: Platelets
Wei-Qing Han, Lian Xu, Xiao-Feng Tang, Wen-Dong Chen, Yong-Jie Wu, Ping-Jin Gao
KEY POINTS: Membrane rafts (MRs)-redox signalling pathway is activated in response to transforming growth factor-β1 (TGF-β1) stimulation in renal tubular cells. This pathway contributes to TGF-1β-induced epithelial-mesenchymal transition (EMT) in renal tubular cells. The the MRs-redox signalling pathway is activated in renal tubular cells isolated from angiotensin II (AngII)-induced hypertensive rats. Inhibition of this pathway attenuated renal inflammation and fibrosis in AngII-induced hypertension...
June 4, 2018: Journal of Physiology
Naomi Terada, Mohammad Rabiul Karim, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
BACKGROUND: β-Catenin is a multi-functional protein involved in nephrogenesis and also plays important roles in renal injury. Here, the expression of β-catenin was investigated in the proximal renal tubular epithelial cells in cisplatin (CDDP)-induced acute kidney injury (AKI) and chronic kidney injury (CKI), because CDDP-induced renal lesions were characterized by proximal renal tubular epithelial degeneration/regeneration and subsequent interstitial fibrosis. METHODS: F344 rats were treated with CDDP...
May 26, 2018: Clinical and Experimental Nephrology
Ola A Harb, Mariem A Elfeky, Basant Sh El Shafaay, Heba F Taha, Gamal Osman, Ibtsam Shehta Harera, Loay M Gertallah, Doaa Metwaly Abdelmonem, Ahmed Embaby
BACKGROUND: Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane...
May 18, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
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