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Fibrosis kidney

Joshua Long, Xavier Vela Parada, Sahir Kalim
Protein carbamylation is a nonenzymatic posttranslational protein modification that can be driven, in part, by exposure to urea's dissociation product, cyanate. In humans, when kidney function is impaired and urea accumulates, systemic protein carbamylation levels increase. Additional mediators of protein carbamylation have been identified including inflammation, diet, smoking, circulating free amino acid levels, and environmental exposures. Carbamylation reactions on proteins are capable of irreversibly changing protein charge, structure, and function, resulting in pathologic molecular and cellular responses...
2018: Advances in Clinical Chemistry
Lifei Gu, Yange Wang, Guolin Yang, Akhtolkhyn Tilyek, Shaoheng Li, Boyang Yu, Chengzhi Chai, Zhengyu Cao
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall (RDP), a folk medicine, has been widely used in Mongolia to treat urinary system diseases. AIM OF THE STUDY: To investigate the effectiveness of RDP on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis and the underlying mechanisms. MATERIALS AND METHODS: A total of 60 mice were randomly divided into six groups: sham group, sham plus RDP (40mg/kg) group, UUO model group, and UUO model plus RDP (10, 20 or 40mg/kg) groups...
October 17, 2018: Journal of Ethnopharmacology
Mareen Matz, Frederik Heinrich, Qiang Zhang, Christine Lorkowski, Evelyn Seelow, Kaiyin Wu, Nils Lachmann, Richard Kwasi Addo, Pawel Durek, Mir-Farzin Mashreghi, Klemens Budde
CONTEXT: Antibody-mediated rejection (ABMR) after kidney transplantation (KTx) remains the crucial obstacle to successful long-term graft function. The identification of gene signatures involved in ABMR could grant the basis for better prevention and treatment strategies. OBJECTIVE: The identification of gene signatures in whole blood cells specific for ABMR after kidney transplantation. MATERIAL AND METHODS: Total RNA from blood cells of 16 kidney transplanted patients with ABMR, stable graft function (SGF) and with T-cell mediated rejection (TCMR) was isolated...
October 20, 2018: Clinical Transplantation
Chengguo Wei, Khadija Banu, Felipe Garzon, John M Basgen, Nimrod Philippe, Zhengzi Yi, Ruijie Liu, Jui Choudhuri, Miguel Fribourg, Tong Liu, Arun Cumpelik, Jenny Wong, Mubeen Khan, Bhaskar Das, Karen Keung, Fadi Salem, Kirk N Campbell, Lewis Kaufman, Paolo Cravedi, Weijia Zhang, Philip J O'Connell, John Cijiang He, Barbara Murphy, Madhav C Menon
BACKGROUND: We previously showed that the presence of a CKD-associated locus in SHROOM3 in a donor kidney results in increased expression of SHROOM3 (an F-actin-binding protein important for epithelial morphogenesis, via rho-kinase [ROCK] binding); this facilitates TGF-b signaling and allograft fibrosis. However, other evidence suggests Shroom3 may have a protective role in glomerular development. METHODS: We used human data, Shroom3 knockdown podocytes, and inducible shRNA-mediated knockdown mice to study the role of Shroom3 in adult glomeruli...
October 19, 2018: Journal of the American Society of Nephrology: JASN
Zhi-Hao Zhang, Jun-Qiu He, Wei-Wei Qin, Ying-Yong Zhao, Ning-Hua Tan
Chronic kidney disease (CKD) has become a major public health problem worldwide and has a great impact on the quality of life of millions of people. Long-term obstructive uropathy is an important cause of CKD. We hypothesized diagnostic biomarkers for early stage obstructive nephropathy can be discovered by metabolomic profiling of biofluid. Unilateral ureteral occlusion (UUO) surgery was performed on rats to induce renal interstitial fibrosis. Sham-operated rats were used as controls. Plasma and urine metabolites were analyzed by UPLC-MS based metabolomic approach...
October 16, 2018: Chemico-biological Interactions
Marco Hatem-Vaquero, Sergio de Frutos, Alicia Luengo, Alba González Abajo, Mercedes Griera, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Laura Calleros
BACKGROUND: Patients with chronic kidney disease present with an accumulation of uraemic toxins, which have been identified as pathogenic agents associated with cardiovascular mortality, which is very high is this patient group. A phenomenon common to the progressive renal dysfunction and associated vascular damage, is the abnormal accumulation of extracellular matrix (ECM) proteins in the renal or vascular structures. OBJECTIVE: To determine the contribution of uraemia or the uraemic toxins to the production of cytokinins and ECM in aortas of uraemic animals or human aortic smooth muscle cells (HASMCs)...
October 15, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Alberto González-Almada, José M Arreola-Guerra, José Argenis López-Sánchez, Eric Cuevas, Mario Vilatoba, Alan G Contreras, Luis E Morales-Buenrostro, Josefina Alberu, Norma O Uribe-Uribe
The association between anti-AT1Rabs and microvascular injury observed in antibody-mediated rejection has been described in kidney graft Biopsies (KGBx). METHODS: We herein describe the histopathologic findings of KGBx performed during the first year of transplantation (Tx) in 134 patients tested for pre-Tx anti-AT1Rabs in cryopreserved sera (04/2009 to 09/2013). Protocol KGBx before implantation (time-zero), 1 year after Tx and for cause KGBx were included. 21/134 Tx patients were anti-AT1Rab positive (≥17 U/mL); 7/21 experienced acute rejection...
October 15, 2018: Transplant Immunology
Ting-Ting Gu, Tian-Yu Chen, Yan-Zi Yang, Xiao-Juan Zhao, Yang Sun, Tu-Shuai Li, Dong-Mei Zhang, Ling-Dong Kong
High dietary fructose is a key causative factor in the development of renal fibrosis. Pterostilbene has anti-fibrotic effect. Understanding the action mechanism of pterostilbene in fructose-induced renal fibrosis remains as a challenge. Here, fructose feeding was found to promote the progress of epithelial-to-mesenchymal transition (EMT) of proximal tubule epithelial cells (PTECs) and collagen deposition in renal cortex of rats with tubulointerstitial fibrosis. Simultaneously, it impaired insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/protein kinase B (Akt) pathway, and increased transforming growth factor-beta 1 (TGF-β1) and TGF-β type I receptor to enhance phosphorylation of drosophila mothers against decapentaplegic homolog 2 (Smad2) and Smad3, and Smad4 expression in rat kidney cortex...
October 15, 2018: European Journal of Pharmacology
Xi Liu, Wei Cao, Jia Qi, Qing Li, Min Zhao, Zhuyun Chen, Jingfeng Zhu, Zhimin Huang, Lin Wu, Bo Zhang, Yanggang Yuan, Changying Xing
Leonurine, a major bioactive component from Herba Leonuri, shows therapeutic potential in several diseases, including diabetes, cardiovascular disease, bovine mastitis and depression. In kidney, it was reported that leonurine was performing a protective effect in both acute kidney injury and renal fibrosis mice models. The aim of this study is to investigate the effect of leonurine in podocyte injury. In the mice model of adriamycin (ADR) -induced nephropathy, the application of leonurine significantly prevented early kidney damage, macrophage infiltration and proteinuria...
October 18, 2018: Free Radical Research
Ye Feng, Yan Liang, Xingwen Zhu, Mingjie Wang, Yuan Gui, Qingmiao Lu, Mengru Gu, Xian Xue, Xiaoli Sun, Weichun He, Junwei Yang, Randy L Johnson, Chunsun Dai
M2 macrophage polarization is known to underlie kidney fibrosis. We previously reported that most of the members of the Wnt family of signaling proteins are induced in fibrotic kidneys. Dysregulation of the signaling protein Wnt5a is associated with fibrosis, but little is known about the role of Wnt5a in regulating M2 macrophage activation that results in kidney fibrosis. Here, using murine Raw 264.7 cells and bone marrow-derived macrophages, we found that Wnt5a enhanced transforming growth factor β1 (TGFβ1)-induced macrophage M2 polarization as well as expression of the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (TAZ)...
October 17, 2018: Journal of Biological Chemistry
Keiko Hosohata, Denan Jin, Shinji Takai, Kazunori Iwanaga
Urinary tract obstruction and the subsequent development of hydronephrosis can cause kidney injuries, which results in chronic kidney disease. Although it is important to detect kidney injuries at an early stage, new biomarkers of hydronephrosis have not been identified. In this study, we examined whether vanin-1 could be a potential biomarker for hydronephrosis. Male Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO). On day 7 after UUO, when the histopathological renal tubular injuries became obvious, the vanin-1 level in the renal pelvic urine was significantly higher than that in voided urine from sham-operated rats...
October 16, 2018: International Journal of Molecular Sciences
Archana Raman, Stephen C Parnell, Yan Zhang, Gail A Reif, Yuqiao Dai, Aditi Khanna, Emily Daniel, Corey White, Jay L Vivian, Darren Paul Wallace
In polycystic kidney disease (PKD), persistent activation of cell proliferation and matrix production contributes to cyst growth and fibrosis, leading to progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is overexpressed by cystic epithelial cells of PKD kidneys. Periostin binds αV β3 -integrins and activates integrin-linked kinase (ILK), leading to Akt/mTOR-mediated proliferation of human PKD cells. By contrast, periostin does not stimulate the proliferation of normal human kidney cells...
October 17, 2018: American Journal of Physiology. Renal Physiology
Grace S Pham, Lei A Wang, Keisa W Mathis
Recent evidence suggests hypertension may be secondary to chronic inflammation that results from hypoactive neuro-immune regulatory mechanisms. To further understand this association, we used systemic lupus erythematosus (SLE) as a model of inflammation-induced hypertension. In addition to prevalent inflammatory kidney disease and hypertension, SLE patients suffer from dysautonomia in the form of decreased efferent vagal tone. Based on this, the cholinergic anti-inflammatory pathway, an endogenous vagus-to-spleen mechanism that when activated results in decreases in systemic inflammation, may be compromised in SLE...
October 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Tuncer Kutlu, Gunay Alcigir
We investigated the pathogenesis of chronic renal fibrosis in cats and dogs using immunohistochemistry. We used the avidin-biotin complex peroxidase (ABC-P) method with antibodies against transforming growth factor-β1, cytokeratin, E-cadherin, S100A4, alpha-smooth muscle actin, vimentin and nestin to determine whether tubule epithelial cells had undergone epithelial-mesenchymal transformation (EMT) that resulted in loss of epithelial cells and an increased number of mesenchymal cells. Although nephrosis was more common in dogs, nephritis was more common in cats; these pathologies developed in both kidneys...
October 17, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Genwen Hu, Zhong Yang, Wen Liang, Caiyong Lai, Yingjie Mei, Yufa Li, Jianmin Xu, Liangping Luo, Xianyue Quan
BACKGROUND: Renal fibrosis is a common consequence of chronic kidney disease (CKD) and is the mechanism by which various forms of CKD progress to endstage renal failure. Accurate assessment of renal fibrosis is important for treatment. PURPOSE: To measure longitudinal changes of intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) before and after reversible unilateral ureteral obstruction in an animal model. STUDY TYPE: Self-controlled animal study...
October 16, 2018: Journal of Magnetic Resonance Imaging: JMRI
Rajkiran Reddy Banala, Satish Kumar Vemuri, Murahari Penkulinti, Gurava Reddy Av, Subbaiah Gpv
Study Design: To induce scoliosis in young female Wistar rats using a noninvasive method and to validate this model. Purpose: To induce scoliosis in a rat model noninvasively by bracing and to study the corresponding gene-expression profile in the spine and different organs. Overview of Literature: Scoliosis involves abnormal lateral curvature of the spine, the causes of which remain unclear. In the literature, it is suggested that scoliosis is genetically heterogeneous, as there are multiple factors involved directly or indirectly in its pathogenesis...
October 18, 2018: Asian Spine Journal
Aliye Uc, Dana K Andersen, Drucy Borowitz, Marshall J Glesby, Julia Mayerle, Robert Sutton, Stephen J Pandol
A workshop was sponsored by the Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, on July 25, 2018, in Pittsburgh, Penn. The workshop was designed to bring together a multidisciplinary group of experts to accelerate the development of therapeutics for clinical application in inflammatory diseases of the exocrine pancreas. Three separate working groups (acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis) were formed to address the needs, gaps, and opportunities...
November 2018: Pancreas
Sandor Koszegi, Agnes Molnar, Lilla Lenart, Judit Hodrea, Dora Bianka Balogh, Tamas Lakat, Edgar Szkibinszkij, Adam Hosszu, Nadja Sparding, Federica Genovese, Laszlo Wagner, Adam Vannay, Attila J Szabo, Andrea Fekete
KEY POINTS SUMMARY: Increased activation of the renin-angiotensin-aldosterone system (RAAS) and elevated growth factor production have crucial importance in the development of renal fibrosis leading to diabetic kidney disease. The aim of this study was to provide evidence for the antifibrotic potential of RAAS inhibitor (RAASi) treatment and to explore the exact mechanism of this protective effect. We found that RAASi ameliorate diabetes-induced renal interstitial fibrosis and decrease profibrotic growth factor production...
October 16, 2018: Journal of Physiology
Hiroki Yoshioka, Tsunemasa Nonogaki, Shiori Fukaya, Yoshimi Ichimaru, Akito Nagatsu, Masae Yoshikawa, Hirohisa Fujii, Makoto Nakao
BACKGROUND: The current study aimed to investigate the hepatoprotective effects of Sasa veitchii extract (SE) on carbon tetrachloride (CCl4 )-induced liver fibrosis in mice. METHODS: Male C57BL/6J mice were intraperitoneally injected with CCl4 dissolved in olive oil (1 g/kg) twice per week for 8 weeks. SE (0.1 mL) was administered orally once per day throughout the study, and body weight was measured weekly. Seventy-two hours after the final CCl4 injection, mice were euthanized and plasma samples were collected...
October 15, 2018: Environmental Health and Preventive Medicine
Hak Joo Lee, Olga Gonzalez, Edward J Dick, Andrew Donati, Denis Feliers, Choudhury Goutam Ghosh, Corinna Ross, Manjeri Venkatachalam, Suzette D Tardif, Balakuntalam S Kasinath
We evaluated whether the marmoset, a nonhuman primate, can serve as a good model to study aging related changes in the kidney by employing healthy young and aged marmosets of both sexes. Aging was associated with glomerulosclerosis, interstitial fibrosis and arteriolosclerosis in both sexes; correspondingly, the content of matrix proteins was increased. Functionally, aging resulted in an increase in urinary albumin and protein excretion. There was a robust correlation between markers of fibrosis and functional changes...
October 13, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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