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Kidney epithelial to mesenchymal transition

Shuyun Liu, Meng Zhao, Yijie Zhou, Chengshi Wang, Yujia Yuan, Lan Li, William Bresette, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
BACKGROUND: Renal fibrosis is the pathological feature of chronic kidney disease (CKD) which leads to end-stage renal disease (ESRD) and renal failure. Resveratrol [3,5,4'-trihydroxy-trans-stilbene (RSV)] has shown benefits for metabolic diseases and anti-cancer therapy, but its potential risk on renal health has not been fully evaluated. PURPOSE: To investigate the global effects of RSV on renal fibrosis in human tubular epithelial cell (TEC) line HK-2, and in mice with unilateral ureteral obstruction (UUO)...
December 17, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Wenbei Han, Qian Ma, Yinglu Liu, Wei Wu, Yue Tu, Lu Huang, Yan Long, Wenwen Wang, Hongyun Yee, Ziyue Wan, Renmao Tang, Yigang Wan, Haitao Tang
BACKGROUND: Huangkui capsule (HKC), an anti-inflammatory Chinese modern patent medicine, has been now widely applied to the clinical therapy of diabetic nephropathy (DN). However, the overall therapeutic mechanisms in vivo are still unclear. Renal tubular epithelial-to-mesenchymal transition (EMT) is one of the major pathogenesis of renal interstitial fibrosis in DN. Recently, the physiological roles of NLRP3 inflammasome activation and toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling are closely linked to EMT...
December 17, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Yihua Wang, Hua Xiong, Dian Liu, Charlotte Hill, Ayse Ertay, Juanjuan Li, Yanmei Zou, Paul Miller, Eileen White, Julian Downward, Robert D Goldin, Xianglin Yuan, Xin Lu
Macroautophagy/autophagy inhibition is a novel anticancer therapeutic strategy, especially for tumors driven by mutant RAS. Here, we demonstrate that autophagy inhibition in RAS-mutated cells induces epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor invasion. This is at least partially achieved by triggering the NFKB/NF-κB pathway via SQSTM1/p62. Knockdown of ATG3 or ATG5 increases oncogenic RAS-induced expression of ZEB1 and SNAI2/Snail2, and activates NFKB activity. Depletion of SQSTM1 abolishes the activation of the NFKB pathway induced by autophagy inhibition in RAS-mutated cells...
February 20, 2019: Autophagy
Ivonne Loeffler
Interstitial fibrosis is a typical feature of end-stage renal diseases, regardless of the initial cause of kidney injury. Epithelial-to-mesenchymal transition (EMT) is a mechanism that is thought to play a role in generating the interstitial matrix-producing myofibroblasts and is prominently induced by the transforming growth factor-β 1 (TGF-β1). TGF-β1 signals through a variety of Smad and non-Smad signaling pathways, including the mitogen-activated protein kinase (MAPK) pathways. In a study published in a recent issue of Clinical Science (Clin...
February 14, 2019: Clinical Science (1979-)
Yajuan Li, Qingsong Hu, Chunlai Li, Ke Liang, Yu Xiang, Heidi Hsiao, Tina K Nguyen, Peter K Park, Sergey D Egranov, Chandrashekar R Ambati, Nagireddy Putluri, David H Hawke, Leng Han, Mien-Chie Hung, Farhad R Danesh, Liuqing Yang, Chunru Lin
Epithelial-mesenchymal transition (EMT) contributes significantly to interstitial matrix deposition in diabetic kidney disease (DKD). However, detection of EMT in kidney tissue is impracticable, and anti-EMT therapies have long been hindered. We reported that phosphatase and tensin homolog (PTEN) promoted transforming growth factor beta 1 (TGF-β), sonic hedgehog (SHH), connective tissue growth factor (CTGF), interleukin 6 (IL-6), and hyperglycemia-induced EMT when PTEN was modified by a MEX3C-catalyzed K27-linked polyubiquitination at lysine 80 (referred to as PTENK27-polyUb)...
February 11, 2019: Journal of Clinical Investigation
Xiao-Yan Xiong, Lin Bai, Shou-Jun Bai, Ya-Kun Wang, Tingting Ji
The phenotypic changes of tubular epithelial cell are hallmark features of renal diseases caused by abnormal uric acid levels. We hereby intend to investigate whether PI3K/p-Akt signaling plays a role in uric-acid induced epithelial-mesenchymal transition process. The normal rat kidney cell line (NRK-52E) was used as a proximal tubular cell model in this study. NRK-52E cells were exposed to different concentrations of uric acid, or PI3K inhibitor LY294002, or both, respectively. The effects of uric acid on cell morphology were examined by phase contrast microscopy, while molecular alternations were assessed by western blot analysis and immunofluorescence staining...
February 10, 2019: Journal of Cellular Physiology
R Ma, J-M Ren, P Li, Y-J Zhou, M-K Zhou, Z Hu, X-Y Xiao
OBJECTIVE: Yes-associated protein (YAP) is a critical factor of Hippo pathway. It can control organ size, regulate proliferation, differentiation, and apoptosis of cells, and mediate epithelial-mesenchymal transition and cell contact inhibition. It has gradually become a hot spot in the field of diabetic nephropathy (DN). Tea domain (TEAD) is a factor with a deoxyribose nucleic acid (DNA) binding domain, which combines with activated YAP to control the expression of their important target factor - connective tissue growth factor (CTGF)...
January 2019: European Review for Medical and Pharmacological Sciences
Sun Ah Nam, Wan-Young Kim, Jin Won Kim, Sang Hee Park, Hong Lim Kim, Myung-Shik Lee, Masaaki Komatsu, Hunjoo Ha, Ji Hee Lim, Cheol Whee Park, Chul Woo Yang, Jin Kim, Yong Kyun Kim
Renal fibrosis is the final common pathway of various renal injuries and it leads to chronic kidney disease. Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death and proliferation. Cellular response during unilateral ureteral obstruction (UUO) is tubular segment specific. Thus the role of autophagy on renal tubulointerstitial fibrosis (TIF) after UUO may be different according to segment of nephron. The role of autophagy during UUO remains unclear especially in distal tubules...
January 28, 2019: Cell Death & Disease
Jin Deng, Yue Xia, Qin Zhou, Xin Wang, Chongxiang Xiong, Xiaofei Shao, Mengjiao Shao, Hequn Zou
BACKGROUND: Chronic renal allograft dysfunction (CRAD) is the main condition affecting the long-term survival of renal allografts. Rosiglitazone, which is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has been shown to exert antifibrotic and anti-inflammatory effects on some renal diseases. The present paper investigates the effect of rosiglitazone on CRAD using a murine model. METHODS: The CRAD group received classical orthotopic F344-Lewis kidney transplantation...
January 22, 2019: Transplant Immunology
Jianhua Xing, Xiaojun Tian
The transition between epithelial and mesenchymal (EMT) is a fundamental cellular process that plays critical roles in development, cancer metastasis, and tissue wound healing. EMT is not a binary process but involves multiple partial EMT states that give rise to a high degree of cell state plasticity. Here, we first reviewed several studies on theoretical predictions and experimental verification of these intermediate states, the role of partial EMT on kidney fibrosis development, and how quantitative signaling information controls cell commitment to partial or full EMT upon transient signals...
January 21, 2019: Physical Biology
Rui Yan, Yuanyuan Wang, Mingjun Shi, Ying Xiao, Lirong Liu, Lingling Liu, Bing Guo
Renal tubular epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) are important pathological features of diabetic nephropathy (DN). However, the regulatory mechanism underlying EMT and TIF are still unclear. Previous studies showed that the decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was closely related to the aggravation of DN, but no published study showed how PTEN participated in the regulation of EMT and TIF. In this study, the rat proximal tubular epithelial cells (NRK52E) and C57BL mice and human kidney tissues were used as the research objects to investigate the mechanism underlying the regulatory effect of peroxisome proliferator-activated receptors γ (PPARγ) on PTEN and its influence on EMT and TIF, the regulation of PTEN's dual activity of lipid phosphatase/protein phosphatase by the serine threonine protein kinase B(AKT)/focal adhesion kinase (FAK) signaling pathway, and the role of PTEN in EMT and TIF...
January 16, 2019: Journal of Cellular Biochemistry
Qian Lu, Wen-Wen Wang, Ming-Zhu Zhang, Zhong-Xuan Ma, Xin-Ran Qiu, Mengli Shen, Xiao-Xing Yin
Oxidative stress has been reported to serve an important role in the development and progression of diabetic nephropathy (DN). Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells promotes renal fibrosis in DN, while the mechanism of reactive oxygen species (ROS)-mediated EMT is not fully understood. The aim of the present study was to investigate the effect of high glucose-induced ROS on the activation of the transforming growth factor (TGF)-β1/phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in a normal rat kidney tubular epithelial cell line (NRK-52E) and rats with type 1 diabetes...
January 2019: Experimental and Therapeutic Medicine
Min Tao, Yingfeng Shi, Lunxian Tang, Yi Wang, Lu Fang, Wei Jiang, Tao Lin, Andong Qiu, Shougang Zhuang, Na Liu
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are serine/threonine kinases and function as regulators of cellular proliferation and differentiation. Recently, we demonstrated that inhibition of ERK1/2 alleviates the development and progression of hyperuricemia nephropathy (HN). However, its potential roles in uric acid-induced tubular epithelial-mesenchymal transition (EMT) and tubular epithelial cell injury are unknown. In this study, we showed that hyperuricemic injury induced EMT as characterized by down-regulation of E-cadherin and up-regulation of Vimentin and Snail1 in a rat model of HN...
January 16, 2019: American Journal of Physiology. Renal Physiology
Lei Chen, Qingling He, Yamin Liu, Yafei Wu, Dongsheng Ni, Jianing Liu, Yanxia Hu, Yuping Gu, Yajun Xie, Qin Zhou, Qianyin Li
PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells. Knock-down of PPP3CB downregulated epithelial marker E-cadherin and upregulated mesenchymal marker Vimentin, promoting the transition of cell states from epithelial to mesenchymal and reorganizing the actin cytoskeleton which contributed to cell migration...
January 11, 2019: International Journal of Molecular Sciences
Yasuhiro Yoshimura, Atsuhiro Taguchi, Shunsuke Tanigawa, Junji Yatsuda, Tomomi Kamba, Satoru Takahashi, Hidetake Kurihara, Masashi Mukoyama, Ryuichi Nishinakamura
BACKGROUND: Previous research has elucidated the signals required to induce nephron progenitor cells (NPCs) from pluripotent stem cells (PSCs), enabling the generation of kidney organoids. However, selectively controlling differentiation of NPCs to podocytes has been a challenge. METHODS: We investigated the effects of various growth factors in cultured mouse embryonic NPCs during three distinct steps of nephron patterning: from NPC to pretubular aggregate, from the latter to epithelial renal vesicle (RV), and from RV to podocyte...
February 2019: Journal of the American Society of Nephrology: JASN
Linghong Lu, Jiajun Zhu, Yaqian Zhang, Yanxia Wang, Shu Zhang, Anzhou Xia
Our previous study demonstrated that febuxostat, a xanthine oxidase inhibitor, can alleviate kidney dysfunction and ameliorate renal tubulointerstitial fibrosis in a rat unilateral ureteral obstruction (UUO) model; however, the underlying mechanisms remain unknown. Increasing evidence has revealed that epithelial‑mesenchymal transition (EMT) is one of the key mechanisms mediating the progression of renal tubulointerstitial fibrosis in chronic kidney disease (CKD). Uterine sensitization‑associated gene‑1 (USAG‑1), a kidney‑specific bone morphogenetic protein antagonist, is involved in the development of numerous types of CKDs...
January 2, 2019: Molecular Medicine Reports
Noemie Jourde-Chiche, Fadi Fakhouri, Laetitia Dou, Jeremy Bellien, Stéphane Burtey, Marie Frimat, Pierre-André Jarrot, Gilles Kaplanski, Moglie Le Quintrec, Vincent Pernin, Claire Rigothier, Marion Sallée, Veronique Fremeaux-Bacchi, Dominique Guerrot, Lubka T Roumenina
The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, which is also fenestrated, transports reabsorbed components and participates in epithelial cell function. The endothelium of large and small vessels supports the renal vasculature...
January 3, 2019: Nature Reviews. Nephrology
Lan Thi Hanh Phi, Ita Novita Sari, Yoseph Toni Wijaya, Kwang Seock Kim, Kichul Park, Art E Cho, Hyog Young Kwon
Ginsenoside Rd is a saponin from ginseng and has been reported to have various biological activities. However, the effect of ginsenoside Rd on the metastasis of colorectal cancer (CRC) remains unknown. Here, we found that ginsenoside Rd decreased the colony-forming ability, migration, invasion, and wound-healing abilities of CRC cells, although it did not affect cell proliferation. In addition, using an inverse-docking assay, we found that ginsenoside Rd bound to epidermal growth factor receptor (EGFR) with a high binding affinity, inducing the downregulation of stemness- and epithelial-mesenchymal transition-related genes; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2...
December 21, 2018: IUBMB Life
Xiejia Li, Hong Liu
Cofilin is a actin-binding protein in eukaryotic cells. It plays a role in maintaining the steady state of the internal environment through regulating actin dynamics, which contributes to the development of various kinds of diseases. In recent 20 years, cofilin has been widely attracted due to its regulatory effect on cell phenotype, gene transcription, apoptosis and inflammation in renal tissue. Cofilin plays a regulatory role in pathological changes in proteinuria diseases such as minimal change nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy...
October 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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
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