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Kidney epithelial to mesenchymal transition

Shan Song, Duojun Qiu, Fengwei Luo, Jinying Wei, Ming Wu, Haijang Wu, Chunyang Du, Yunxia Du, Yunzhuo Ren, Nan Chen, Huijun Duan, Yonghong Shi
Tubular injury is one of the crucial determinants of progressive renal failure in diabetic nephropathy (DN), while epithelial-to-mesenchymal transition (EMT) of tubular cells contributes to the accumulation of matrix protein in the diabetic kidney. Activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome leads to the maturation of interleukin (IL)-1B and is involved in the pathogenic mechanisms of diabetes. In this study, we explored the role of NLRP3 inflammasome on high glucose (HG) or transforming growth factor-B1 (TGFB1)-induced EMT in HK-2 cells...
October 1, 2018: Journal of Molecular Endocrinology
Jiming Yin, Yangjia Wang, Jing Chang, Bin Li, Jia Zhang, Yu Liu, Song Lai, Ying Jiang, Huihua Li, Xiangjun Zeng
The epithelial-mesenchymal transition (EMT) of podocytes had been reported to be involved in the glomerular fibrosis in diabetic kidney diseases, which was regulated by TGFβ and NFκB pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGFβ in polycystic kidney disease and attenuate EMT in renal tubular cells. Therefore, it is hypothesized that apelin might inhibit the EMT of podocytes through downregulating the expression and activation of TGFβ/Smad pathway in diabetic kidney diseases...
October 9, 2018: Cell Death & Disease
Yohei Sekino, Naoya Sakamoto, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Thang Pham Quoc, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Fumi Kawakami, Jose A Karam, Kanishka Sircar, Akio Matsubara, Wataru Yasui
BACKGROUND: The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC. METHODS: Expression of Uc...
October 4, 2018: BMC Cancer
Chung-Ming Chen, Shu-Hui Juan, Hsiu-Chu Chou
INTRODUCTION: The renin-angiotensin system and epithelial-mesenchymal transition play crucial roles in the development of kidney fibrosis. The connection between the renin-angiotensin system and transforming growth factor-β in epithelial-mesenchymal transition remains largely unknown. MATERIALS AND METHODS: We assessed oxidative stress, cytokine levels, renal morphology, profibrotic growth factor and renin-angiotensin system component expression, and cell-specific E- and N-cadherin expression in the kidneys of gerbils with streptozotocin-induced diabetes mellitus...
July 2018: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Lan Thi Hanh Phi, Yoseph Toni Wijaya, Ita Novita Sari, Ying-Gui Yang, Yun Kyung Lee, Hyog Young Kwon
Ginsenoside Rb2, a saponin from Panax ginseng, has been shown to have many functions. However, the effect of ginsenoside Rb2 on the metastasis of colorectal cancer (CRC) remains unknown. CRC cell lines HT29 and SW620 were used to determine the effects of ginsenoside Rb2 on the colony-forming, migration, invasion, and wound-healing abilities of CRC cells in vitro. Further, ginsenoside Rb2 was given intraperitoneally at 5 mg/kg of mouse body weight to check its effect on the metastasis of CRC cells in vivo. Ginsenoside Rb2 decreased colony-forming ability, migration, invasion, and wound healing of CRC cells in vitro, although it did not affect cell proliferation...
September 27, 2018: Cancer Medicine
Mei Xue, Ying Cheng, Fei Han, Yunpeng Chang, Yang Yang, Xiaoyu Li, Li Chen, Yunhong Lu, Bei Sun, Liming Chen
Triptolide possesses the trait of renal protection. Epithelial-mesenchymal transition (EMT) is closely linked to the pathogenesis of diabetic kidney disease (DKD). MicroRNAs have recently emerged as critical regulators of DKD. However, it is poorly understood whether triptolide alleviates renal EMT by regulating microRNAs in DKD. In this study, we found that triptolide decreased albuminuria, improved the renal structure and reduced renal EMT in rats with DKD. Furthermore, activation of the PI3K/AKT signaling pathway was increased in diabetic rats, which was partly reversed by triptolide...
2018: International Journal of Biological Sciences
Kexin Hua, Yangjie Li, Hufeng Zhou, Xueying Hu, Yushan Chen, Rongrong He, Rui Luo, Rui Zhou, Dingren Bi, Hui Jin
In this study, animal experimentation verified that the canonical Wnt/β-catenin signaling pathway was activated under a reduced activity of p-β-catenin (Ser33/37/Thr41) and an increased accumulation of β-catenin in the lungs and kidneys of pigs infected with a highly virulent strain of H. parasuis . In PK-15 and NPTr cells, it was also confirmed that infection with a high-virulence strain of H. parasuis induced cytoplasmic accumulation and nuclear translocation of β-catenin. H. parasuis infection caused a sharp degradation of E-cadherin and an increase of the epithelial cell monolayer permeability, as well as a broken interaction between β-catenin and E-cadherin dependent on Wnt/β-catenin signaling pathway...
2018: Frontiers in Cellular and Infection Microbiology
Yan-Rong Liu, Bo Sun, Guo-Hong Zhu, Wei-Wei Li, Yi-Xuan Tian, Lu-Meng Wang, Shu-Min Zong, Peng-Zhen Sheng, Meng Li, Shuang Chen, Yuan Qin, Hui-Juan Liu, Hong-Gang Zhou, Tao Sun, Cheng Yang
BACKGROUND: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier...
September 18, 2018: Toxicology and Applied Pharmacology
John W Stanifer, Heather M Stapleton, Tomokazu Souma, Ashley Wittmer, Xinlu Zhao, L Ebony Boulware
BACKGROUND AND OBJECTIVES: Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018...
September 13, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Yu-Wei Chang, Kamaleshwar P Singh
Arsenic contamination is a significant public health issue, and kidney is one of the target organ for arsenic-induced adverse effects. Renal fibrosis is a well-known pathological stage frequently observed in progressive chronic kidney disease (CKD). Epidemiological studies implicate arsenic exposure to CKD, but the role of arsenic in kidney fibrosis and the underlying mechanism is still unclear. It is in this context that the current study evaluated the effects of long-term arsenic exposure on the cellular response in morphology, and marker genes expression with respect to fibrosis using human kidney 2 (HK-2) epithelial cells...
September 7, 2018: Journal of Cellular Physiology
Bodokhsuren Tsogbadrakh, Kyung Don Ju, Jinho Lee, Miyeun Han, Junga Koh, Yeonsil Yu, Hajeong Lee, Kyung-Sang Yu, Yun Kyu Oh, Hyo Jin Kim, Curie Ahn, Kook-Hwan Oh
BACKGROUND: Renal fibrosis is characterized by excessive production and deposition of extracellular matrix (ECM), which leads to progressive renal failure. Adenosine-monophosphate-activated protein kinase (AMPK) is a highly conserved kinase that plays a key role in Smad-3 signaling. Here, we examined the effect of a novel AMPK activator, HL156A, on the inhibition of renal fibrosis in in vivo and in vitro models. METHODS: Unilateral ureteral obstruction (UUO) was induced in male Wistar rats...
2018: PloS One
Yijie Jia, Zongji Zheng, Yanlin Yang, Meina Zou, Jimin Li, Ling Wang, Meiping Guan, Yaoming Xue
Accumulating evidence indicates that proteinuria promotes the progression of diabetic kidney disease (DKD) and induces renal epithelial tubular cell epithelial-to-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress, but the mechanism remains unclear. In our previous research, we found that miR-4756 levels were increased in the urinary extracellular vesicles of type 2 diabetes mellitus patients with macroalbuminuria. In a preliminary study, we found that miR-4756 may be derived from renal tubular epithelial cells, but its role has not been elucidated...
August 26, 2018: Journal of Cellular Physiology
Xin-Fang Wang, Bei-Hao Zhang, Xiao-Qing Lu, Rui-Qiang Wang
Between 1% and 15% of people are globally affected by kidney stones, and this disease has become more common since the 1970s. Therefore, this study aims to investigate the effects of gastrin-releasing peptide receptor (GRPR) gene silencing via the PI3K/Akt signaling pathway on the development of the epithelial-mesenchymal transition (EMT) and formation of a calcium oxalate crystal in renal tubular epithelial cells (TECs) of kidney stones. A total of 70 clean and healthy C57BL/6J mice were assigned into the normal ( n = 10) and kidney stones groups ( n = 60)...
August 24, 2018: Journal of Cellular Physiology
Jack S Lawson, Hui-Hsuan Liu, Harriet M Syme, Robert Purcell, Caroline P D Wheeler-Jones, Jonathan Elliott
Chronic kidney disease (CKD) is common in both geriatric cats and aging humans, and is pathologically characterised by chronic tubulointerstitial inflammation and fibrosis in both species. Cats with CKD may represent a spontaneously occurring, non-rodent animal model of human disease, however little is known of feline renal cell biology. In other species, TGF-β1 signalling in the proximal tubular epithelium is thought to play a key role in the initiation and progression of renal fibrosis. In this study, we first aimed to isolate and characterise feline proximal tubular epithelial cells (FPTEC), comparing them to human primary renal epithelial cells (HREC) and the human proximal tubular cell line HK-2...
2018: PloS One
Zhengchao Wang, Qing Zhu, Weili Wang, Junping Hu, Pin-Lan Li, Fan Yi, Ningjun Li
MicroRNA (miR) 429 has been shown to inhibit epithelial-to-mesenchymal transition (EMT) in cancer cells. However, the role of miR429 in EMT in non-cancer cells has not been defined, especially in the kidneys. The present study determined whether miR429 participated in angiotensin (ANG) II-induced EMT and fibrogenesis in renal cells. In NRK-52E cells, a rat proximal tubular cell line, incubation of ANG II (10-9 M) for 24 h significantly reduced the level of miR429 by 60%, and meanwhile increased the protein levels of mesenchymal markers α-smooth muscle actin and fibroblast-specific protein-1 by 3 fold and decreased epithelial marker E-cadherin by 60%, which was blocked by Losartan, a AT1 receptor antagonist...
August 22, 2018: American Journal of Physiology. Renal Physiology
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...
September 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
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