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https://www.readbyqxmd.com/read/28460073/regulation-of-mir-29b-and-mir-30c-by-vitamin-d-receptor-activators-contributes-to-attenuate-uraemia-induced-cardiac-fibrosis
#1
Sara Panizo, Natalia Carrillo-López, Manuel Naves-Díaz, Guillermo Solache-Berrocal, Laura Martínez-Arias, Raúl R Rodrigues-Díez, Amalia Fernández-Vázquez, Carlos Martínez-Salgado, Marta Ruiz-Ortega, Adriana Dusso, Jorge B Cannata-Andía, Isabel Rodríguez
Background.: Uraemic cardiomyopathy, a process mainly associated with increased myocardial fibrosis, is the leading cause of death in chronic kidney disease patients and can be prevented by vitamin D receptor activators (VDRAs). Since some microRNAs (miRNAs) have emerged as regulators of the fibrotic process, we aimed to analyse the role of specific miRNAs in VDRA prevention of myocardial fibrosis as well as their potential use as biomarkers. Methods.: Wistar rats were nephrectomized and treated intraperitoneally with equivalent doses of two VDRAs: calcitriol and paricalcitol...
April 28, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28452949/generation-and-applications-of-a-dna-aptamer-against-gremlin-1
#2
Qian Li, Yongwei Huo, Yonghong Guo, Xiaoyan Zheng, Wengang Sun, Zhiming Hao
Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein, plays important roles in diverse biological processes including early embryonic development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which are RNA or DNA single-stranded oligonucleotides capable of binding specifically to different targets ranging from small organics to whole cells, have potential applications in targeted imaging, diagnosis and therapy. In this study, we obtained a DNA aptamer against Gremlin-1 (G-ap49) using in vitro Systematic Evolution of Ligands by Exponential Enrichment (SELEX)...
April 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28446517/a-novel-%C3%AE-calcitonin-gene-related-peptide-analogue-protects-against-end-organ-damage-in-experimental-hypertension-cardiac-hypertrophy-and-heart-failure
#3
Aisah A Aubdool, Pratish Thakore, Fulye Argunhan, Sarah-Jane Smillie, Moritz Schnelle, Salil Srivastava, Khadija M Alawi, Elena Wilde, Jennifer Mitchell, Keith Farrell-Dillon, Daniel A Richards, Giuseppe Maltese, Richard C Siow, Manasi Nandi, James E Clark, Ajay M Shah, Anette Sams, Susan D Brain
Background -Research into the therapeutic potential of α-calcitonin gene-related peptide (α-CGRP) has been limited due to its peptide nature and short half-life. Here, we evaluate whether a novel potent and long lasting (t½ ≥ 7h) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28414804/cyclosporine-a-alters-expression-of-renal-micrornas-new-insights-into-calcineurin-inhibitor-nephrotoxicity
#4
Jennifer L Gooch, Clayton King, Cynthia E Francis, Paul S Garcia, Yun Bai
Calcineurin inhibitors are powerful immunosuppressants that revolutionized organ transplantation. However, non-immune effects of the calcineurin inhibitor, such as cyclosporine A (CsA), have significantly hindered their use. Specifically, nephrotoxicity, which is associated with tubulointerstitial fibrosis, inflammation, and podocyte damage, affects up to half of all transplant patients. Calcineurin is involved in many aspects of kidney development and function; therefore, mechanisms of CsA-induced nephrotoxicity are complex and not yet fully understood...
2017: PloS One
https://www.readbyqxmd.com/read/28352334/long-non-coding-rna-asncmtrna-2-is-upregulated-in-diabetic-kidneys-and-high-glucose-treated-mesangial-cells
#5
Yan Gao, Zhao-Yu Chen, Yan Wang, Yan Liu, Jian-Xia Ma, Yu-Kun Li
Diabetic nephropathy (DN) is one of the most frequent complications associated with type I and II diabetes mellitus. Kidneys from patients with DN are characterized by mesangial matrix expansion and increased thickness of the glomerular basement membrane, which are induced by reactive oxygen species (ROS) production. Previous studies have been conducted to investigate this; however, the detailed mechanism of DN progression remains to be elucidated. The present study evaluated the expression of antisense mitochondrial non-coding RNA-2 (ASncmtRNA-2) in an experimental DN model and cultured human mesangial cells...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28339906/interstitial-fibrosis-scored-on-whole-slide-digital-imaging-of-kidney-biopsies-is-a-predictor-of-outcome-in-proteinuric-glomerulopathies
#6
Laura H Mariani, Sebastian Martini, Laura Barisoni, Pietro A Canetta, Jonathan P Troost, Jeffrey B Hodgin, Matthew Palmer, Avi Z Rosenberg, Kevin V Lemley, Hui-Ping Chien, Jarcy Zee, Abigail Smith, Gerald B Appel, Howard Trachtman, Stephen M Hewitt, Matthias Kretzler, Serena M Bagnasco
Background.: Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. Methods.: We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37)...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#7
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not exclusively established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28237649/protein-kinase-ck2%C3%AE-catalytic-subunit-ameliorates-diabetic-renal-inflammatory-fibrosis-via-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Junying Huang, Zhiquan Chen, Jie Li, Qiuhong Chen, Jingyan Li, Wenyan Gong, Jiani Huang, Peiqing Liu, Heqing Huang
Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA)...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28151474/lincrna-gm4419-knockdown-ameliorates-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-mediated-inflammation-in-diabetic-nephropathy
#9
Hong Yi, Rui Peng, Lu-Yu Zhang, Yan Sun, Hui-Min Peng, Han-Deng Liu, Li-Juan Yu, Ai-Ling Li, Ya-Juan Zhang, Wen-Hao Jiang, Zheng Zhang
Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28118775/renoprotective-effects-of-a-dipeptidyl-peptidase-4-inhibitor-in-a-mouse-model-of-progressive-renal-fibrosis
#10
Takahiro Uchida, Takashi Oda, Hidehito Matsubara, Atsushi Watanabe, Hanako Takechi, Naoki Oshima, Yutaka Sakurai, Hiroo Kumagai
Although the effects of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond their hypoglycemic action have been reported, whether these inhibitors have renoprotective effects in nondiabetic chronic kidney disease (CKD) is unclear. We examined the therapeutic effects of DPP-4 inhibition in mice with unilateral ureteral obstruction (UUO), a nondiabetic model of progressive renal fibrosis. After UUO surgery, mice were administered either the DPP-4 inhibitor alogliptin or a vehicle by oral gavage once a day for 10 days...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28109003/eradication-of-hcv-and-non-liver-related-non-aids-related-events-in-hiv-hcv-coinfection
#11
Juan Berenguer, Elena Rodríguez-Castellano, Ana Carrero, Miguel A Von Wichmann, Marta Montero, María J Galindo, Josep Mallolas, Manuel Crespo, María J Téllez, Carmen Quereda, José Sanz, Carlos Barros, Cristina Tural, Ignacio Santos, Federico Pulido, Josep M Guardiola, Rafael Rubio, Enrique Ortega, María L Montes, Juan J Jusdado, Gabriel Gaspar, Herminia Esteban, José M Bellón, Juan González-García
We assessed non-liver-related non-AIDS-related (NLR-NAR) events and mortality in a cohort of HIV/HCV-coinfected patients treated with interferon and ribavirin between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and non-responders. Fine and Gray regression analysis was conducted to determine the adjusted sub-hazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk...
January 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28099916/involvement-of-nf-%C3%AE%C2%BAbiz-and-related-cytokines-in-age-associated-renal-fibrosis
#12
Ki Wung Chung, Hyeong Oh Jeong, Bonggi Lee, Daeui Park, Dae Hyun Kim, Yeun Ja Choi, Eun Kyeong Lee, Kyung Mok Kim, June Whoun Park, Byung Pal Yu, Hae Young Chung
Chronic inflammation is a major contributor to age-related nephropathic changes, including renal fibrosis. In this study, various experimental paradigms were designed to delineate the role played by NF-κBIZ (also known as IκBζ) in age-associated renal fibrosis. Analyses based on RNA-sequencing findings obtained by next generation sequencing (NGS) revealed the upregulations of NF-κBIZ and of IL-6 and MCP-1 (both known to be regulated by NF-κBIZ) during aging. The up-regulation of NF-κBIZ in aged rat kidneys coincided with increased macrophage infiltration...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28089974/cardiopulmonary-disease-development-in-anti-rna-polymerase-iii-positive-systemic-sclerosis-comparative-analyses-from-an-unselected-prospective-patient-cohort
#13
Anna-Maria Hoffmann-Vold, Øyvind Midtvedt, Anders H Tennøe, Torhild Garen, May Brit Lund, Trond M Aaløkken, Arne K Andreassen, Fadi Elhage, Cathrine Brunborg, Eli Taraldsrud, Øyvind Molberg
OBJECTIVE: Extensive skin disease and renal crisis are hallmarks of anti-RNA polymerase III (RNAP)-positive systemic sclerosis (SSc), while lung and heart involvement data are conflicting. Here, the aims were to perform time-course analyses of interstitial lung disease (ILD) and pulmonary hypertension (PH) in the RNAP subset of a prospective unselected SSc cohort and to use the other autoantibody subsets as comparators. METHODS: The study cohort included 279 patients with SSc from the observational Oslo University Hospital cohort with complete data on (1) SSc-related autoantibodies, (2) paired, serial analyses of lung function and fibrosis by computed tomography, and (3) PH verified by right heart catheterization...
January 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28077323/high-glucose-down-regulates-microrna-181a-5p-to-increase-pro-fibrotic-gene-expression-by-targeting-early-growth-response-factor-1-in-hk-2-cells
#14
Ping Xu, Mei-Ping Guan, Jian-Gang Bi, Dan Wang, Zong-Ji Zheng, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor β1 (TGF-β1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27849555/role-of-post-transcriptional-regulation-of-mrna-stability-in-renal-pathophysiology-focus-on-chronic-kidney-disease
#15
REVIEW
Eva Feigerlová, Shyue-Fang Battaglia-Hsu
Chronic kidney disease (CKD) represents an important public health problem. Its progression to end-stage renal disease is associated with increased morbidity and mortality. The determinants of renal function decline are not fully understood. Recent progress in the understanding of post-transcriptional regulation of mRNA stability has helped the identification of both the trans- and cis-acting elements of mRNA as potential markers and therapeutic targets for difficult-to-diagnose and -treat diseases, including CKDs such as diabetic nephropathy...
November 14, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27706206/incidences-and-risk-factors-of-organ-manifestations-in-the-early-course-of-systemic-sclerosis-a-longitudinal-eustar-study
#16
Veronika K Jaeger, Elina G Wirz, Yannick Allanore, Philipp Rossbach, Gabriela Riemekasten, Eric Hachulla, Oliver Distler, Paolo Airò, Patricia E Carreira, Alexandra Balbir Gurman, Mohammed Tikly, Serena Vettori, Nemanja Damjanov, Ulf Müller-Ladner, Jörg H W Distler, Mangtao Li, Ulrich A Walker
OBJECTIVE: Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc. METHODS: In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset...
2016: PloS One
https://www.readbyqxmd.com/read/27703201/rhein-reversal-of-dna-hypermethylation-associated-klotho-suppression-ameliorates-renal-fibrosis-in-mice
#17
Qin Zhang, Shasha Yin, Lin Liu, Zhihong Liu, Wangsen Cao
Renal fibrosis is the hallmark of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications. Rhein, a plant-derived anthraquinone, displays strong anti-fibrosis properties, but its protective mode of action remains incompletely understood. Here we explore the mechanism of Rhein anti-renal fibrosis by investigating its regulation of Klotho, a known renal anti-fibrotic protein whose suppression after renal injury reportedly involves aberrant DNA methylation...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27693697/let-7d-mirna-prevents-tgf-%C3%AE-1-induced-emt-and-renal-fibrogenesis-through-regulation-of-hmga2-expression
#18
Ya Wang, Ying Le, Jun-Yu Xue, Zong-Ji Zheng, Yao-Ming Xue
TGF-β1-induced epithelial to mesenchymal transition (EMT) process of tubular epithelial cells plays a leading role in the occurrence and progression of renal fibrosis as seen in diabetic nephropathy (DN). High mobility group AT-hook 2 (HMGA2) is considered to be involved in TGF-β1-mediated EMT via multifactorial mechanisms. Specific microRNAs (miRNAs) are closely associated with EMT, and here we focused on let-7d miRNA as a regulator of HMGA2. This study aims to investigate the effects of HMGA2 on EMT process induced by TGF-β1 using small interfering RNA (siRNA) technique in vitro, and further explore the potential role of let-7d miRNA during renal fibrosis in DN...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27617141/genetic-considerations-in-pediatric-chronic-kidney-disease
#19
REVIEW
Lyndsay A Harshman, Diana Zepeda-Orozco
Chronic kidney disease (CKD) in children is an irreversible process that, in some cases, may lead to end-stage renal disease. The majority of children with CKD have a congenital disorder of the kidney or urological tract arising from birth. There is strong evidence for both a genetic and epigenetic component to progression of CKD. Utilization of gene-mapping strategies, ranging from genome-wide association studies to single-nucleotide polymorphism analysis, serves to identify potential genetic variants that may lend to disease variation...
March 2016: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/27616741/fyn-deficiency-attenuates-renal-fibrosis-by-inhibition-of-phospho-stat3
#20
Hye-Young Seo, Jae-Han Jeon, Yun-A Jung, Gwon-Soo Jung, Eun Ju Lee, Young-Keun Choi, Keun-Gyu Park, Mi Sun Choe, Byoung Kuk Jang, Mi-Kyung Kim, In-Kyu Lee
The hallmark of renal tubulointerstitial fibrosis is the accumulation of myofibroblasts and extracellular matrix proteins. Fyn, a member of the Src family of kinases, has diverse biological functions including regulation of mitogenic signaling and proliferation and integrin-mediated interaction. Src family proteins promote pulmonary fibrosis by augmenting transforming growth factor-β signaling, but their role in renal fibrosis is less understood. We observed upregulation of Fyn in a renal fibrosis model induced by unilateral ureteral obstruction...
September 8, 2016: Kidney International
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