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https://www.readbyqxmd.com/read/29127220/therapeutic-potential-of-micrornas-for-the-treatment-of-renal-fibrosis-and-ckd
#1
Wenshan Lv, Fan Fan, Yangang Wang, Ezekiel Gonzalez-Fernandez, Chen Wang, Lili Yang, George W Booz, Richard J Roman
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29102563/tgf-%C3%AE-mediates-renal-fibrosis-via-the-smad3-erbb4-ir-long-noncoding-rna-axis
#2
Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29062612/lncrna-h19-is-involved-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-bovine-epithelial-cells-through-pi3k-akt-signaling-pathway
#3
Wei Yang, Xuezhong Li, Shaopei Qi, Xueru Li, Kun Zhou, Suzhu Qing, Yong Zhang, Ming-Qing Gao
Increased levels of long noncoding RNA H19 (H19) have been observed in many inflammatory and organ fibrosis diseases including ulcerative colitis, osteoarthritis, liver fibrosis, renal fibrosis and pulmonary fibrosis. However, the role of H19 in bovine mastitis and mastitis-caused fibrosis is still unclear. In our study, H19 was characterized as a novel regulator of EMT induced by transforming growth factor-β1 (TGF-β1) in bovine mammary alveolar cell-T (MAC-T) cell line. We found that H19 was highly expressed in bovine mastitis tissues and inflammatory MAC-T cells induced by virulence factors of pathogens...
2017: PeerJ
https://www.readbyqxmd.com/read/29058957/ctgf-is-expressed-during-cystic-remodeling-in-the-pkd-mhm-cy-rat-model-for-autosomal-dominant-polycystic-kidney-disease-adpkd
#4
Stefan Gauer, Yvonne Holzmann, Bettina Kränzlin, Sigrid C Hoffmann, Norbert Gretz, Ingeborg A Hauser, Margarete Goppelt-Struebe, Helmut Geiger, Nicholas Obermüller
Connective tissue growth factor (CTGF, also named CCN2) plays an important role in the development of tubulointerstitial fibrosis, which most critically determines the progression to end-stage renal failure in autosomal-dominant polycystic kidney disease (ADPKD), the most common genetically caused renal disease. We determined CTGF expression in a well-characterized animal model of human ADPKD, the PKD/Mhm (cy/+) rat. Kidneys of 12 weeks old (cy/+) as well as (+/+) non-affected rats were analyzed for CTGF RNA and protein expression by RT-PCR, Northern and Western blot analyses, in situ hybridization, and IHC...
October 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29042082/the-proto-oncogene-tyrosine-protein-kinase-src-is-essential-for-macrophage-myofibroblast-transition-during-renal-scarring
#5
Patrick Ming-Kuen Tang, Shuang Zhou, Chun-Jie Li, Jinyue Liao, Jun Xiao, Qing-Ming Wang, Guang-Yu Lian, Jinhong Li, Xiao-Ru Huang, Ka-Fai To, Chi-Fai Ng, Charing Ching-Ning Chong, Ronald Ching-Wa Ma, Tin-Lap Lee, Hui-Yao Lan
Src activation has been associated with fibrogenesis after kidney injury. Macrophage-myofibroblast transition is a newly identified process to generate collagen-producing myofibroblasts locally in the kidney undergoing fibrosis in a TGF-β/Smad3-dependent manner. The potential role of the macrophage-myofibroblast transition in Src-mediated renal fibrosis is unknown. In studying this by RNA sequencing at single-cell resolution, we uncovered a unique Src-centric regulatory gene network as a key underlying mechanism of macrophage-myofibroblast transition...
October 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28986222/auf1-modulates-tgf-%C3%AE-signal-in-renal-tubular-epithelial-cells-via-post-transcriptional-regulation-of-nedd4l-expression
#6
Jing Yan, Feng Du, Sheng-Dong Li, Ye Yuan, Jing-Yi Jiang, Si Li, Xin-Yu Li, Zhen-Xian Du
Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models. While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion mediated by TGF-β was significantly compromised...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28976873/inflammatory-biomarkers-and-liver-histopathology-in-non-uremic-and-uremic-chronic-hepatitis-c-patients
#7
Bengu Tatar, Sukran Kose, Emel Pala, Erhan Tatar
BACKGROUND: The aim of this study is to investigate the association between hepatic activity index (HAI) and fibrosis score (FS) with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. METHODS: Fifty chronic hepatitis C (cHepC) positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group...
2017: Acta Medica (Hradec Králové)
https://www.readbyqxmd.com/read/28931758/molecular-characterization-of-the-transition-from-acute-to-chronic-kidney-injury-following-ischemia-reperfusion
#8
Jing Liu, Sanjeev Kumar, Egor Dolzhenko, Gregory F Alvarado, Jinjin Guo, Can Lu, Yibu Chen, Meng Li, Mark C Dessing, Riana K Parvez, Pietro E Cippà, A Michaela Krautzberger, Gohar Saribekyan, Andrew D Smith, Andrew P McMahon
Though an acute kidney injury (AKI) episode is associated with an increased risk of chronic kidney disease (CKD), the mechanisms determining the transition from acute to irreversible chronic injury are not well understood. To extend our understanding of renal repair, and its limits, we performed a detailed molecular characterization of a murine ischemia/reperfusion injury (IRI) model for 12 months after injury. Together, the data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, and molecular and cellular characterization of targeted gene activity provide a comprehensive profile of injury, repair, and long-term maladaptive responses following IRI...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28809130/long-noncoding-rna-a-new-contributor-and-potential-therapeutic-target-in-fibrosis
#9
Xiaoying Jiang, Fujun Zhang
Fibrosis is the excess deposition of extracellular matrix components which occur in multiple organs and ultimately leads to organ failure. Long noncoding RNAs (lncRNAs) are a kind of noncoding RNAs longer than approximately 200 nucleotides with no protein-encoding capacity. A growing body of evidence suggests that lncRNAs are also involved in tissues fibrosis in several organs, such as lungs fibrosis, liver fibrosis, renal fibrosis and cardiac fibrosis. In this review, we summarized the current studies of lncRNAs in the process of fibrosis and hopefully aid in better understanding the molecular mechanism of fibrosis and provide a basis to explore new therapeutic targets of fibrosis...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28780716/epigenetics-a-potential-key-mechanism-involved-in-the-pathogenesis-of-cardiorenal-syndromes
#10
REVIEW
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Massimo de Cal, Claudio Ronco
Epigenetics is defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, including higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. Recently, much attention has been paid to the role and the function of epigenetics and epimutations in the cellular and subcellular pathways and in the regulation of genes in the setting of both kidney and cardiovascular disease...
August 5, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28762541/real-world-effectiveness-and-safety-of-paritaprevir-ritonavir-ombitasvir-and-dasabuvir-with-or-without-ribavirin-for-patients-with-chronic-hepatitis-c-virus-genotype-1b-infection-in-taiwan
#11
Chen-Hua Liu, Chun-Jen Liu, Tung-Hung Su, Hung-Chih Yang, Chun-Ming Hong, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
BACKGROUND AND AIM: The real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) remain limited for East Asian hepatitis C virus genotype 1b (HCV-1b) patients. We aimed to evaluate the anti-viral responses of PrOD-based regimens for HCV-1b patients in Taiwan. METHODS: We performed a retrospective analysis of 103 HCV-1b patients receiving PrOD with or without ribavirin (RBV) for 12 weeks. Data were analyzed to assess the on-treatment and off-therapy HCV viral load, and on-treatment adverse events (AEs)...
August 1, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28703905/successful-treatment-of-chronic-hepatitis-c-infection-with-directly-acting-antivirals-in-renal-transplant-recipients
#12
Sunil Taneja, Ajay Duseja, Arka De, Vivek Kumar, Raja Ramachandran, Ashish Sharma, Radha K Dhiman, Krishan L Gupta, Yogesh Chawla
AIMS: The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. Aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. METHODS: A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016...
July 13, 2017: Nephrology
https://www.readbyqxmd.com/read/28676554/diabetic-rats-present-higher-urinary-loss-of-proteins-and-lower-renal-expression-of-megalin-cubilin-clc-5-and-cftr
#13
Miriam F Figueira, Raquel C Castiglione, Carolina M de Lemos Barbosa, Felipe M Ornellas, Geórgia da Silva Feltran, Marcelo M Morales, Rodrigo N da Fonseca, Jackson de Souza-Menezes
Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28662883/paritaprevir-ritonavir-ombitasvir-plus-dasabuvir-with-ribavirin-for-treatment-of-recurrent-chronic-hepatitis-c-genotype-1-infection-after-liver-transplantation-real-world-experience
#14
Ming-Lung Yu, Yao-Li Chen, Chung-Feng Huang, Kuo-Hua Lin, Ming-Lun Yeh, Ching-I Huang, Meng-Hsuan Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang
BACKGROUND/AIMS: The registered trial has demonstrated that paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) with ribavirin was effective for recurrent hepatitis C virus genotype 1 (HCV-1) infection after liver transplantation in patients with mild fibrosis; however, the real-world efficacy and safety of this regimen have not been determined. METHODS: The efficacy (sustained virological response, SVR12, undetectable HCV RNA 12 weeks post-treatment) and safety were evaluated in 12 patients with recurrent HCV-1 infection after liver transplantation...
June 26, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28620300/novel-anti-fibrotic-therapies
#15
REVIEW
Benita L McVicker, Robert G Bennett
Fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease, as well as a post-injury response that drives progression. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Novel treatments have recently been identified that hold promise as potential therapeutic agents for cardiovascular diseases associated with fibrosis, as well as other fibrotic conditions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28620270/flucytosine-and-amphotericin-b-coadministration-induces-dose-related-renal-injury
#16
Alexandra Folk, Cornel Balta, Hildegard Herman, Alexandra Ivan, Oana Maria Boldura, Lucian Paiusan, Aurel Ardelean, Anca Hermenean
Invasive fungal infections remain an important clinical problem, and despite recent approaches, they bring high morbidity and mortality. Combination therapies are the most effective; however, adverse effects need to be considered. In this study, we aimed to evaluate the nephrotoxicity induced by combined therapy of flucytosine (FL) and amphotericin B (AMF) at 3 different doses administered to mice for 14 days: 300 μg/kg AMF+50 mg/kg FL; 600 μg/kg AMF+100 mg/kg FL; 900 μg/kg AMF+150 mg/kg FL. Antifungal coadministration triggered nuclear translocation of NF-κB and upregulated nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65 (NF-κB p65) messenger RNA mRNA level in dose-dependent manner...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28618421/identification-of-tisp40-as-an-essential-regulator-of-renal-tubulointerstitial-fibrosis-via-tgf-%C3%AE-smads-pathway
#17
Cheng-Cheng Xiao, Jie Zhang, Peng-Cheng Luo, Cong Qin, Yang Du, Jin-Zhuo Ning, Hai-Zhou Zheng
BACKGROUND: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. METHODS: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT) and the underlying molecular mechanisms in transforming growth factor-β (TGF-β)-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R) by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28611273/racial-disparities-in-hepatitis-c-treatment-eligibility
#18
Omar Sims, David Pollio, Barry Hong, Carol North
BACKGROUND: Hepatitis C (HCV) is more prevalent in African Americans than in any other racial group in the United States. However, African Americans are more likely to be deemed ineligible for HCV treatment than non-African Americans. There has been limited research into the origins of racial disparities in HCV treatment eligibility. AIM: The purpose of this study was to compare medical and non-medical characteristics commonly assessed in clinical practice that could potentially contribute to HCV treatment ineligibility disparities between African American and non-African American patients...
July 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28596300/clear-cell-renal-cell-carcinoma-is-linked-to-epithelial-to-mesenchymal-transition-and-to-fibrosis
#19
Lea Landolt, Øystein Eikrem, Philipp Strauss, Andreas Scherer, David H Lovett, Christian Beisland, Kenneth Finne, Tarig Osman, Mohammad M Ibrahim, Gro Gausdal, Lavina Ahmed, James B Lorens, Jean Paul Thiery, Tuan Zea Tan, Miroslav Sekulic, Hans-Peter Marti
Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq(®) Access library preparation protocol and TruSeq Small RNA library preparation kit...
June 2017: Physiological Reports
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
#20
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
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