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https://www.readbyqxmd.com/read/27927603/lysophosphatidic-acid-signaling-through-its-receptor-initiates-profibrotic-epithelial-cell-fibroblast-communication-mediated-by-epithelial-cell-derived-connective-tissue-growth-factor
#1
Norihiko Sakai, Jerold Chun, Jeremy S Duffield, David Lagares, Takashi Wada, Andrew D Luster, Andrew M Tager
The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA1-deficient (LPA1(-/-)) or -sufficient (LPA1(+/+)) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts...
December 4, 2016: Kidney International
https://www.readbyqxmd.com/read/27925186/up-regulation-of-transient-receptor-potential-melastatin-6-channel-expression-by-tumor-necrosis-factor-%C3%AE-in-the-presence-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor
#2
Chisa Furukawa, Naoko Fujii, Aya Manabe, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Yoshinori Ito, Masahiko Yamaguchi, Yasuhiro Yamazaki, Akira Ikari
Anti-epidermal growth factor receptor (EGFR) drugs such as erlotinib and gefitinib cause a side effect of hypomagnesemia, but chemotherapy to treat this has not yet been developed. The transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of Mg(2+) in the renal tubule. We reported previously that the expression of TRPM6 is up-regulated by epidermal growth factor (EGF) in renal tubular epithelial NRK-52E and HEK293 cells. EGF-induced elevation of TRPM6 expression was inhibited by erlotinib, gefitinib, and lapatinib...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924516/carbon-monoxide-inhibits-the-nuclear-cytoplasmic-translocation-of-hmgb1-in-an-in-vitro-oxidative-stress-injury-model-of-mouse-renal-tubular-epithelial-cells
#3
Yu Jia, Lu Wang, Guang-Yuan Zhao, Zhi-Qiang Wang, Song Chen, Gang Chen
Carbon monoxide (CO), as a vital small molecule in signaling pathways, is found to be involved in ischemia-reperfusion injury (IRI) in renal transplantation. CO-releasing molecule-2 (CORM-2), a CO-releasing molecule, is a type of metal carbonyl complexes which can quickly release CO in vivo. In this study, an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein (HMGB1) in mouse primary renal proximal tubular epithelial cells (RPTECs)...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27916883/enhanced-autophagy-in-polycystic-kidneys-of-aqp11-null-mice
#4
Yasuko Tanaka, Mayumi Watari, Tatsuya Saito, Yoshiyuki Morishita, Kenichi Ishibashi
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(-/-) kidneys...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27882940/mdm2-prevents-spontaneous-tubular-epithelial-cell-death-and-acute-kidney-injury
#5
Dana Thomasova, Martrez Ebrahim, Kristina Fleckinger, Moying Li, Jakob Molnar, Bastian Popper, Helen Liapis, Ahmed M Kotb, Florian Siegerist, Nicole Endlich, Hans-Joachim Anders
Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27880866/tgf-%C3%AE-1-stimulates-movement-of-renal-proximal-tubular-epithelial-cells-in-a-three-dimensional-cell-culture-via-an-autocrine-tgf-%C3%AE-2-production
#6
Deyi Luo, Qiunong Guan, Kunjie Wang, Christopher Y C Nguan, Caigan Du
TGF-βs are multifunctional cytokines, but their roles in human renal homeostasis are not fully understood. This study investigated the role of TGF-β1 in the movement of human renal proximal tubular epithelial cells (PTECs) in a three-dimensional (3D) model. HKC-8 cells, a human PTEC line, were grown in a 3D collagen culture system. Cell movement was observed under a microscope. The gene expression was examined using PCR Arrays or qRT-PCR, and protein levels by Western blot. Here, we showed that the tight junction structure formed between adjacent cells of a HKC-8 cell colony in 3D cultures, and TGF-β1 stimulated their movement, evidenced by the appearance of fingerlike pseudopodia in the leader cells at the edge of the colonies...
November 20, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27872161/identification-of-urinary-exosomal-non-coding-rnas-as-novel-biomarkers-in-chronic-kidney-disease
#7
Rimpi Khurana, Glory Ranches, Simon Schafferer, Melanie Lukasser, Michael Rudnicki, Gert Mayer, Alexander Hüttenhofer
In chronic kidney disease (CKD), the decline in glomerular filtration rate is associated with increased morbidity and mortality and thus poses a major challenge for healthcare systems. While the contribution of tissue-derived miRNAs and mRNAs to CKD progression has extensively been studied, little is known about the role of urinary exosomes and their association with CKD. Exosomes are small, membrane-derived endocytic vesicles that contribute to cell-to-cell communication and are present in various body fluids, such as blood or urine...
November 21, 2016: RNA
https://www.readbyqxmd.com/read/27863213/tubular-cytoplasmic-expression-of-snai1-in-renal-transplant-biopsies-a-sign-of-diseased-epithelial-phenotype
#8
Marco Prunotto, Lyubov Chaykovska, Massimo Bongiovanni, Milo Frattini, Thomas Cagarelli, Franziska Weibel, Maurizio Bruschi, Antonio Garcia de Herreros, Solange Moll
The aim of the present study was to analyze in vivo the role of SNAI1 on renal fibrosis. Unilateral ureteral obstruction injury was induced in Snai1 knockout mice. Snai1 gene deletion was, however, only partial and could therefore not be correlated to reduced fibrosis. Expression of SNAI1 protein and epithelial-mesenchymal transformation markers was then assessed in human chronic allograft nephropathy biopsy specimens. Significant up-regulation of SNAI1 protein was detected within cytoplasm of proximal tubules localized, for some of them, near foci of fibrosis and tubular atrophy...
November 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27855304/therapeutic-activity-of-the-histone-deacetylase-inhibitor-sb939-on-renal-fibrosis
#9
Sun-Woo Kang, Soung-Min Lee, Joo-Yong Kim, So-Yeon Kim, Yeong-Hoon Kim, Tae-Hee Kim, Mi-Seon Kang, Won-Hee Jang, Su-Kil Seo
Fibrosis is the final pathological outcome of many chronic kidney diseases and is quite common. Thus, development of effective anti-fibrotic agents is urgently needed. Although histone deacetylases (HDACs) have been reported to be involved in renal fibrosis, current HDAC inhibitors are unsatisfactory anti-fibrosis drugs. Therefore, more potentially relevant anti-renal fibrosis HDAC inhibitors are needed. We initially found that non-cytotoxic concentrations of SB939 (pracinostat) had strong anti-fibrotic activity, drastically decreasing TGF-β1-induced alpha smooth muscle actin (α-SMA) expression in the NRK renal fibroblast cell line...
November 14, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27848094/aminoglycoside-induced-nephrotoxicity-in-children
#10
REVIEW
Stephen J McWilliam, Daniel J Antoine, Rosalind L Smyth, Munir Pirmohamed
Aminoglycoside antibiotics, in particular gentamicin and tobramycin, are still commonly used in paediatric clinical practice. These drugs cause nephrotoxicity, which particularly affects the proximal tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides via the multi-ligand receptor megalin. Recent epidemiological studies, using more widely accepted definitions of acute kidney injury (AKI), have suggested that AKI may occur in between 20 and 33 % of children exposed to aminoglycosides...
November 15, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27834856/stearoyl-coa-desaturase-1-protects-cells-against-lipotoxicity-mediated-apoptosis-in-proximal-tubular-cells
#11
Tamaki Iwai, Shinji Kume, Masami Chin-Kanasaki, Shogo Kuwagata, Hisazumi Araki, Naoko Takeda, Takeshi Sugaya, Takashi Uzu, Hiroshi Maegawa, Shin-Ichi Araki
Saturated fatty acid (SFA)-related lipotoxicity is a pathogenesis of diabetes-related renal proximal tubular epithelial cell (PTEC) damage, closely associated with a progressive decline in renal function. This study was designed to identify a free fatty acid (FFA) metabolism-related enzyme that can protect PTECs from SFA-related lipotoxicity. Among several enzymes involved in FFA metabolism, we identified stearoyl-CoA desaturase-1 (SCD1), whose expression level significantly decreased in the kidneys of high-fat diet (HFD)-induced diabetic mice, compared with non-diabetic mice...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27821911/acute-alloxan-toxicity-causes-granulomatous-tubulointerstitial-nephritis-with-severe-mineralization
#12
Lianshan Zhang, Yui Terayama, Taiki Nishimoto, Yasushi Kodama, Kiyokazu Ozaki
Alloxan had been recognized as having a direct nephrotoxic effect different from its diabetogenic action. We encountered previously unreported granulomatous tubulointerstitial nephritis with severe luminal and interstitial mineralization in one diabetic rat after one week of alloxan administration. Histopathologically, many dilated and occluded proximal and distal tubules were segmentally observed in the cortex and outer medulla. The tubular lumen contained minerals and cell debris. Tubular epithelial cells were degenerated and piled up, and they protruded into the lumen, where they enveloped minerals...
October 2016: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/27815996/human-airway-organoid-engineering-as-a-step-toward-lung-regeneration-and-disease-modeling
#13
Qi Tan, Kyoung Moo Choi, Delphine Sicard, Daniel J Tschumperlin
Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27780843/binding-of-anti-dsdna-antibodies-to-proximal-tubular-epithelial-cells-contribute-s-to-renal-tubulo-interstitial-inflammation
#14
Susan Yung, Claudia Yc Ng, Kin Yi Au, Kwok Fan Cheung, Qing Zhang, Chenzhu Zhang, Desmond Yh Yap, Mel Km Chau, Tak Mao Chan
Immune deposits are often observed along the tubular basement membrane in patients with lupus nephritis, but the role of anti-dsDNA antibody deposition on tubulo-interstitial inflammation remains to be investigated. We examined the effect of human polyclonal anti-dsDNA antibodies on inflammatory processes in cultured proximal renal tubular epithelial cells (HK-2 cells) and their association with serum levels of IL-6, IL-8 and MCP-1 in patients. Binding of anti-dsDNA antibodies to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry...
October 25, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27763560/renal-protective-effects-of-17%C3%AE-estradiol-on-mice-with-acute-aristolochic-acid-nephropathy
#15
Min Shi, Liang Ma, Li Zhou, Ping Fu
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury...
October 18, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27756181/silencing-hif-1%C3%AE-aggravates-growth-inhibition-and-necrosis-of-proximal-renal-tubular-epithelial-cell-under-hypoxia
#16
Yue Chen, Suhua Jiang, Jianzhou Zou, Yihong Zhong, Xiaoqiang Ding
The kidney is particularly susceptible to ischemia/hypoxia insult while dysfunction of proximal tubular epithelial cells (PTEC) is a primary pathologic hallmark in acute kidney injury. Hypoxia-inducible factor-1 (HIF-1) is a key regulator responsible for cellular hypoxic responses. Therefore, we investigated the effects of HIF-1 suppression, using small interference RNA (siRNA), upon the cell fate of PTEC under hypoxia, and explored the underlying possible molecular mechanism. Hypoxia was induced with hypoxia mimetic cobalt chloride...
October 19, 2016: Renal Failure
https://www.readbyqxmd.com/read/27735870/a-high-content-screening-assay-to-identify-compounds-with-anti-epithelial-mesenchymal-transition-effects-from-the-chinese-herbal-medicine-tong-mai-yang-xin-wan
#17
Ningning Liu, Lailai Li, Xin Zhu, Zhiqiang Ling, Jianguo Feng, Ying Hu, Yi Wang, Lijun Mou, Yi Wang
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27725720/bioprinting-of-3d-convoluted-renal-proximal-tubules-on-perfusable-chips
#18
Kimberly A Homan, David B Kolesky, Mark A Skylar-Scott, Jessica Herrmann, Humphrey Obuobi, Annie Moisan, Jennifer A Lewis
Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen...
October 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27703192/gdf11-improves-tubular-regeneration-after-acute-kidney-injury-in-elderly-mice
#19
Ying Zhang, Qinggang Li, Dong Liu, Qi Huang, Guangyan Cai, Shaoyuan Cui, Xuefeng Sun, Xiangmei Chen
The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia-reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2'-deoxyuridine (EdU)-positive proximal tubular epithelial cells...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27692564/release-of-extracellular-dna-influences-renal-ischemia-reperfusion-injury-by-platelet-activation-and-formation-of-neutrophil-extracellular-traps
#20
Marcel P B Jansen, Diba Emal, Gwendoline J D Teske, Mark C Dessing, Sandrine Florquin, Joris J T H Roelofs
Acute kidney injury is often the result of ischemia reperfusion injury, which leads to activation of coagulation and inflammation, resulting in necrosis of renal tubular epithelial cells. Platelets play a central role in coagulation and inflammatory processes, and it has been shown that platelet activation exacerbates acute kidney injury. However, the mechanism of platelet activation during ischemia reperfusion injury and how platelet activation leads to tissue injury are largely unknown. Here we found that renal ischemia reperfusion injury in mice leads to increased platelet activation in immediate proximity of necrotic cell casts...
September 27, 2016: Kidney International
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