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Rna renal fibrosis

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
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
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
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
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
Nicolas Melis, Isabelle Rubera, Marc Cougnon, Sébastien Giraud, Baharia Mograbi, Amine Belaid, Didier F Pisani, Stephan M Huber, Sandra Lacas-Gervais, Konstantina Fragaki, Nicolas Blondeau, Paul Vigne, Christian Frelin, Thierry Hauet, Christophe Duranton, Michel Tauc
The eukaryotic initiation factor 5A (eIF5A), which is highly conserved throughout evolution, has the unique characteristic of post-translational activation through hypusination. This modification is catalyzed by two enzymatic steps involving deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Notably, eIF5A may be involved in regulating the lifespan of Drosophila during long-term hypoxia. Therefore, we investigated the possibility of a link between eIF5A hypusination and cellular resistance to hypoxia/anoxia...
September 9, 2016: Journal of the American Society of Nephrology: JASN
Haiyan Fu, Yuan Tian, Lili Zhou, Dong Zhou, Roderick J Tan, Donna B Stolz, Youhua Liu
Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium...
September 9, 2016: Journal of the American Society of Nephrology: JASN
Agnieszka Loboda, Mateusz Sobczak, Alicja Jozkowicz, Jozef Dulak
Renal fibrosis, irrespective of its etiology, is a final common stage of almost all chronic kidney diseases. Increased apoptosis, epithelial-to-mesenchymal transition, and inflammatory cell infiltration characterize the injured kidney. On the molecular level, transforming growth factor-β1 (TGF-β1)-Smad3 signaling pathway plays a central role in fibrotic kidney disease. Recent findings indicate the prominent role of microRNAs, small noncoding RNA molecules that inhibit gene expression through the posttranscriptional repression of their target mRNAs, in different pathologic conditions, including renal pathophysiology...
2016: Mediators of Inflammation
Shuping Wei, Chaoli Xu, Joshua J Rychak, Alice Luong, Yu Sun, Zhijian Yang, Mingxia Li, Chunrui Liu, Ninghua Fu, Bin Yang
The purpose of this study was to evaluate whether ultrasound-targeted microbubble destruction transfer of interfering RNA against connective tissue growth factor (CTGF) in the kidney would ameliorate renal fibrosis in vivo. A short hairpin RNA (shRNA) targeting CTGF was cloned into a tool plasmid and loaded onto the surface of a cationic microbubble product. A unilateral ureteral obstruction (UUO) model in mice was used to evaluate the effect of CTGF knockdown. Mice were administered the plasmid-carrying microbubble intravenously, and ultrasound was applied locally to the obstructed kidney...
September 3, 2016: Ultrasound in Medicine & Biology
In Hee Kim, Jun Xu, Xiao Liu, Yukinori Koyama, Hsiao-Yen Ma, Karin Diggle, Young-Hyun You, Jan M Schilling, Dilip Jeste, Kumar Sharma, David A Brenner, Tatiana Kisseleva
We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction...
August 2016: Age (2005-)
Veena Roberts, B Lu, J Chia, P J Cowan, K M Dwyer
Chronic kidney disease has multiple etiologies, but its single, hallmark lesion is renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of ATP and increased CD39 activity on regulatory T cells (Treg) is protective in adriamycin-induced renal fibrosis. We examined the effect of overexpression of human CD39 on the development of renal fibrosis in the unilateral ureteric obstructive (UUO) model, a model widely used to study the molecular and cellular factors involved in renal fibrosis. Mice overexpressing human CD39 (CD39Tg) and their wild-type (WT) littermates were subjected to UUO; renal histology and messenger RNA (mRNA) levels of adenosine receptors and markers of renal fibrosis were examined up to 14 days after UUO...
August 26, 2016: Purinergic Signalling
Solenne Tillet, Sébastien Giraud, Thomas Kerforne, Thibaut Saint-Yves, Sandrine Joffrion, Jean-Michel Goujon, Jerôme Cau, Gérard Mauco, Maurice Petitou, Thierry Hauet
Coagulation is an important pathway in the pathophysiology of ischemia-reperfusion injuries. In particular, deceased after circulatory death (DCD) donors undergo a no-flow period, a strong activator of coagulation. Hence, therapies influencing the coagulation cascade must be developed. We evaluated the effect of a new highly specific and effective anti-Xa/IIa molecule, with an integrated innovative antidote site (EP217609), in a porcine preclinical model mimicking injuries observed in DCD donor kidney transplantation...
July 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Pei-Fang Hsieh, Shu-Fen Liu, Tsung-Jen Hung, Chien-Ya Hung, Guo-Zheng Liu, Lea-Yea Chuang, Mei-Fen Chen, Jue-Long Wang, Ming-Der Shi, Chen Hung Hsu, Yow-Ling Shiue, Yu-Lin Yang
Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-β1 (TGF-β1), after which the levels of various fibrogenic markers (e...
September 10, 2016: Experimental Cell Research
Ting He, Jiachuan Xiong, Ling Nie, Yanlin Yu, Xu Guan, Xinli Xu, Tangli Xiao, Ke Yang, Liang Liu, Daohai Zhang, Yunjian Huang, Jingbo Zhang, Junping Wang, Kumar Sharma, Jinghong Zhao
: Renal interstitial fibrosis is a major pathologic feature of diabetic nephropathy, while the pathogenesis and therapeutic interventions of diabetic renal interstitial fibrosis are not well established. In this study, we first demonstrated that high glucose could induce renal fibroblast (NRK-49F) cell proliferation and activation to myofibroblasts, accompanied by a significant increase in the intracellular levels of reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)...
August 4, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Sin Y Choi, Hae J Kee, Thomas Kurz, Finn K Hansen, Yuhee Ryu, Gwi R Kim, Ming Q Lin, Li Jin, Zhe H Piao, Myung H Jeong
Epithelial-mesenchymal transition (EMT) and renal fibrosis are closely involved in chronic kidney disease. Inhibition of histone deacetylase (HDAC) has an anti-fibrotic effect in various diseases. However, the pathophysiological role of isoform-specific HDACs or class-selective HDACs in renal fibrosis remains unknown. Here, we investigated EMT markers and extracellular matrix (ECM) proteins in a human proximal tubular cell line (HK-2) by using HDAC inhibitors or by knockdown of class I HDACs (HDAC1, 2, 3 and 8)...
July 15, 2016: Journal of Cellular and Molecular Medicine
Hong Xie, Jing-Dong Xue, Feng Chao, Yan-Feng Jin, Qiang Fu
Although long non-coding RNAs (lncRNAs) are important players in the initiation and progression of many pathological processes, the role of lncRNAs in renal fibrosis still remains unclear. We showed that lncRNA-H19 expression was significantly up-regulated in TGF-β2-induced HK-2 cell fibrosis and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo. H19 knockdown significantly attenuated renal fibrosis in vitro and in vivo. LncRNA-H19, miR-17, and fibronectin constituted to a regulatory network involved in renal fibrosis...
July 6, 2016: Oncotarget
Philip F Halloran, Konrad S Famulski, Jeff Reeve
Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis...
September 2016: Nature Reviews. Nephrology
Chao-Hung Chen, Liang-Yin Ke, Hua-Chen Chan, An-Sheng Lee, Kun-Der Lin, Chih-Sheng Chu, Mei-Yueh Lee, Pi-Jung Hsiao, Chin Hsu, Chu-Huang Chen, Shyi-Jang Shin
Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells...
August 2016: Journal of Lipid Research
Eleni Arvaniti, Panagiotis Moulos, Athina Vakrakou, Christos Chatziantoniou, Christos Chadjichristos, Panagiotis Kavvadas, Aristidis Charonis, Panagiotis K Politis
Transcriptome analysis by RNA-seq technology allows novel insights into gene expression and regulatory networks in health and disease. To better understand the molecular basis of renal fibrosis, we performed RNA-seq analysis in the Unilateral Ureteric Obstruction (UUO) mouse model. We analysed sham operated, 2- and 8-day post-ligation renal tissues. Thousands of genes with statistical significant changes in their expression were identified and classified into cellular processes and molecular pathways. Many novel protein-coding genes were identified, including critical transcription factors with important regulatory roles in other tissues and diseases...
2016: Scientific Reports
Tara K Sigdel, Oriol Bestard, Nathan Salomonis, Szu-Chuan Hsieh, Joan Torras, Maarten Naesens, Tim Q Tran, Silke Roedder, Minnie M Sarwal
BACKGROUND: Polyomavirus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. To identify PVAN-specific gene expression and underlying molecular mechanisms, we analyzed kidney biopsies with and without PVAN. METHODS: The study included 168 posttransplant renal allograft biopsies (T cell-mediated rejection [TCMR] = 26, PVAN = 10, normal functioning graft = 73, and interstitial fibrosis/tubular atrophy = 59) from 168 unique kidney allograft recipients...
October 2016: Transplantation
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