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Kidney epithelial to mesenchymal transition

Maaike Waasdorp, Dennis M de Rooij, Sandrine Florquin, JanWillem Duitman, C Arnold Spek
End-stage renal disease, the final stage of all chronic kidney disorders, is associated with renal fibrosis and inevitably leads to renal failure and death. Transition of tubular epithelial cells (TECs) into mesenchymal fibroblasts constitutes a proposed mechanism underlying the progression of renal fibrosis and here we assessed whether protease-activated receptor (PAR)-1, which recently emerged as an inducer of epithelial-to-mesenchymal transition (EMT), aggravates renal fibrosis. We show that PAR-1 activation on TECs reduces the expression of epithelial markers and simultaneously induces mesenchymal marker expression reminiscent of EMT...
November 28, 2018: Journal of Cellular and Molecular Medicine
Juan Jin, Meiyu Ye, Kang Hu, Jianguan Gong, Qiang He
BACKGROUND: Diabetic nephropathy (DN) is a serious complication in diabetic patients and has been considered as the main cause of end-stage renal disease. However, there are no studies on the role of stromal interaction molecule (STIM) and its two subtypes, STIM1 and STIM2, in the epithelial-to-mesenchymal transition (EMT) of podocytes induced by diabetic kidney disease (DKD). The present study suggests for the first time that STIM inhibition decreases DKD-induced EMT. METHODS: All DKD patients were diagnosed based on renal biopsies carried out at the Department of Nephrology, Zhejiang Provincial People's Hospital and selected using the Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN...
November 26, 2018: Histology and Histopathology
Sheng Zhao, Jun-Tao Jiang, Deng Li, Yi-Ping Zhu, Shu-Jie Xia, Bang-Min Han
We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in renal fibrosis in male offspring; however, the underlying mechanism governing this effect has not been thoroughly elucidated to date. We hypothesized that DBP exposure induces TGF-β expression and abnormal activation of epithelial-mesenchymal transition (EMT) in fibrotic kidneys. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14-18. In the DBP-exposed group, immunohistochemistry (IHC) staining showed increased expression of TGF-β1 and EMT markers...
November 16, 2018: Ecotoxicology and Environmental Safety
Yifan Li, Yanqing Gong, Xianghui Ning, Ding Peng, Libo Liu, Shiming He, Kan Gong, Cuijian Zhang, Xuesong Li, Liqun Zhou
BACKGROUND: Metastasis is the primary cause of death in renal cell carcinoma (RCC). Loss of cell-to-cell adhesion, including tight junctions (TJs) is the initial step in the process of metastasis. Claudin-7 (CLDN7) is a major component of TJs. However, the clinical significance and its regulation of kidney tumorigenesis remain poorly understood. METHODS: A total of 120 fresh clear cell RCC (ccRCC) specimens and 144 primary RCC and adjacent nonmalignant renal paraffin specimens were obtained from Department of Urology, Peking University First Hospital...
November 14, 2018: Journal of Experimental & Clinical Cancer Research: CR
Ourania S Kotsiou, Konstantinos I Gourgoulianis, Sotirios G Zarogiannis
Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis...
2018: Frontiers in Immunology
Laura Marquez-Exposito, Carolina Lavoz, Raul R Rodrigues-Diez, Sandra Rayego-Mateos, Macarena Orejudo, Elena Cantero-Navarro, Alberto Ortiz, Jesús Egido, Rafael Selgas, Sergio Mezzano, Marta Ruiz-Ortega
Chronic kidney disease (CKD) is emerging as an important health problem due to the increase number of CKD patients and the absence of an effective curative treatment. Gremlin has been proposed as a novel therapeutic target for renal inflammatory diseases, acting via Vascular Endothelial Growth Factor Receptor-2 (VEGFR2). Although many evidences suggest that Gremlin could regulate renal fibrosis, the receptor involved has not been yet clarified. Gremlin, as other TGF-β superfamily members, regulates tubular epithelial to mesenchymal transition (EMT) and, therefore, could contribute to renal fibrosis...
2018: Frontiers in Pharmacology
Maja Životić, Björn Tampe, Gerhard Müller, Claudia Müller, Aleksandar Lipkovski, Xingbo Xu, Gunsmaa Nyamsuren, Michael Zeisberg, Jasmina Marković-Lipkovski
Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor 1 (FGFR1) cross-talk have been involved in epithelial-to-mesenchymal transition (EMT) process during carcinogenesis. Since EMT also contributes to maladaptive repair and parenchymal damage during renal fibrosis, we became encouraged to explore the role of NCAM/FGFR1 signaling as initiating or driving forces of EMT program in cultured human proximal tubular epithelial cells (TECs). TECs stimulated with TGF-β1 (10ng/mL) was used as an established in vitro EMT model...
2018: PloS One
Cyrina D van Beusekom, Tanja M Zimmering
OBJECTIVES: The aim of this study was to evaluate the role of angiotensin II (AT-II) and its main mediator, transforming growth factor beta 1 (TGF-β1), in the development of feline renal fibrosis. METHODS: Expression of marker genes indicating epithelial-to-mesenchymal transition (EMT), profibrotic mediators and matricellular proteins was measured in feline kidney epithelial cells (Crandell Rees feline kidney [CRFK] cells) after incubation with AT-II and/or TGF-β1...
October 22, 2018: Journal of Feline Medicine and Surgery
Ting-Ting Gu, Tian-Yu Chen, Yan-Zi Yang, Xiao-Juan Zhao, Yang Sun, Tu-Shuai Li, Dong-Mei Zhang, Ling-Dong Kong
High dietary fructose is a key causative factor in the development of renal fibrosis. Pterostilbene has anti-fibrotic effect. Understanding the action mechanism of pterostilbene in fructose-induced renal fibrosis remains as a challenge. Here, fructose feeding was found to promote the progress of epithelial-to-mesenchymal transition (EMT) of proximal tubule epithelial cells (PTECs) and collagen deposition in renal cortex of rats with tubulointerstitial fibrosis. Simultaneously, it impaired insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/protein kinase B (Akt) pathway, and increased transforming growth factor-beta 1 (TGF-β1) and TGF-β type I receptor to enhance phosphorylation of drosophila mothers against decapentaplegic homolog 2 (Smad2) and Smad3, and Smad4 expression in rat kidney cortex...
October 16, 2018: European Journal of Pharmacology
Keiko Hosohata, Denan Jin, Shinji Takai, Kazunori Iwanaga
Urinary tract obstruction and the subsequent development of hydronephrosis can cause kidney injuries, which results in chronic kidney disease. Although it is important to detect kidney injuries at an early stage, new biomarkers of hydronephrosis have not been identified. In this study, we examined whether vanin-1 could be a potential biomarker for hydronephrosis. Male Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO). On day 7 after UUO, when the histopathological renal tubular injuries became obvious, the vanin-1 level in the renal pelvic urine was significantly higher than that in voided urine from sham-operated rats...
October 16, 2018: International Journal of Molecular Sciences
Yuchang Zhou, Yong Zhang, Dahai Zhu
BACKGROUND: Myostatin (MSTN), a member of the transforming growth factor-β (TGF-β) superfamily, has been implicated in the negative regulation of skeletal myogenesis. However, the molecular mechanism through which MSTN regulates early embryonic myogenesis is not well understood. RESULTS: We demonstrate that MSTN regulates early embryonic myogenesis by promoting the epithelial-to-mesenchymal transition (EMT) of the dermomyotome during somitogenesis in chicks. We show that the MSTN gene is first expressed at the center of the dermomyotome...
December 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Shan Song, Duojun Qiu, Fengwei Luo, Jinying Wei, Ming Wu, Haijiang 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...
November 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...
October 8, 2018: Clinical Journal of the American Society of Nephrology: CJASN
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