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https://www.readbyqxmd.com/read/29324897/serum-galactose-deficient-iga1-and-igg-autoantibodies-correlate-in-patients-with-iga-nephropathy
#1
William J Placzek, Hiroyuki Yanagawa, Yuko Makita, Matthew B Renfrow, Bruce A Julian, Dana V Rizk, Yusuke Suzuki, Jan Novak, Hitoshi Suzuki
IgA nephropathy is an autoimmune disease characterized by IgA1-containing glomerular immune deposits. We previously proposed a multi-hit pathogenesis model in which patients with IgA nephropathy have elevated levels of circulatory IgA1 with some O-glycans deficient in galactose (Gd-IgA1, autoantigen). Gd-IgA1 is recognized by anti-glycan IgG and/or IgA autoantibodies, resulting in formation of pathogenic immune complexes. Some of these immune complexes deposit in the kidney, activate mesangial cells, and incite glomerular injury leading to clinical presentation of IgA nephropathy...
2018: PloS One
https://www.readbyqxmd.com/read/29324237/dna-induction-of-mdm2-promotes-proliferation-of-human-renal-mesangial-cells-and-alters-peripheral-b-cells-subsets-in-pediatric-systemic-lupus-erythematosus
#2
Chen-Xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-Yuan Wang, Lan-Fang Cao, Wei Zhou, Tong-Xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC)...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29322432/renal-histopathological-findings-of-retinal-vasculopathy-with-cerebral-leukodystrophy
#3
Yutaka Tsubata, Takashi Morita, Tetsuo Morioka, Taiji Sasagawa, Kouzo Ikarashi, Noriko Saito, Hisaki Shimada, Shigeru Miyazaki, Shinji Sakai, Hajime Tanaka, Rie Saito, Yasuko Toyoshima, Hiroaki Nozaki, Ichiei Narita
Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare autosomal dominant systemic microvascular disease. Neurological disorders and visual disturbance are highlighted as manifestations of RVCL; however, there are few reports focused on nephropathy. Herein, we describe detailed renal histopathological findings in a daughter and father with RVCL, proven by TREX1 genetic analysis. A kidney biopsy of the daughter, 35-year-old with asymptomatic proteinuria, revealed unique and various glomerular changes...
January 10, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29320847/new-insights-into-the-role-of-renal-resident-cells-in-the-pathogenesis-of-lupus-nephritis
#4
Seung-Ki Kwok, George C Tsokos
Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. The immunopathogenesis of SLE is complex and most clinical trials of biologics targeting immune cells or their mediators have failed to show efficacy in SLE patients. It has therefore become increasingly clear that additional, local factors give rise to the inflammation and organ damage...
January 12, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29315280/gremlin-regulates-podocyte-apoptosis-via-transforming-growth-factor-%C3%AE-tgf-%C3%AE-pathway-in-diabetic-nephropathy
#5
Xiao-Bing Wang, Hong Zhu, Wei Song, Jian-Hua Su
BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-β (TGF-β) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting...
January 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29311647/-pro-renin-receptor-is-involved-in-mesangial-fibrosis-and-matrix-expansion
#6
Kaori Narumi, Emiko Sato, Takuo Hirose, Tae Yamamoto, Takashi Nakamichi, Mariko Miyazaki, Hiroshi Sato, Sadayoshi Ito
(Pro)renin receptor [(P)RR] is expressed in the kidney and is involved in renal injury. Although (P)RR is activated by indoxyl sulfate (IS) and may be related to renal injury, the details remain unclear. We used mouse mesangial cell line SV40 MES13 to investigate the association of (P)RR with mesangial fibrosis or expansion. Furthermore, we examined the correlation between serum soluble (P)RR [s(P)RR] and various laboratory data including serum IS, a uremic toxin that induces renal fibrosis through (P)RR, and pathological indices in chronic kidney disease and particularly in IgA nephropathy patients...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29299781/slit2-robo1-signaling-is-involved-in-angiogenesis-of-glomerular-endothelial-cells-exposed-to-a-diabetic-like-environment
#7
Junhui Liu, Weiping Hou, Tao Guan, Luyao Tang, Xufei Zhu, Yi Li, Shihui Hou, Jun Zhang, Hua Chen, Yunjian Huang
Abnormal angiogenesis plays a pathological role in diabetic nephropathy (DN), contributing to glomerular hypertrophy and microalbuminuria. Slit2/Robo1 signaling participates in angiogenesis in some pathological contexts, but whether it is involved in glomerular abnormal angiogenesis of early DN is unclear. The present study evaluated the effects of Slit2/Robo1 signaling pathway on angiogenesis of human renal glomerular endothelial cells (HRGECs) exposed to a diabetic-like environment or recombinant Slit2-N...
January 3, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29290980/up-regulation-of-5-lipoxygenase-by-inhibition-of-cathepsin-g-enhances-trail-induced-apoptosis-through-down-regulation-of-survivin
#8
Seon Min Woo, Kyoung-Jin Min, Seung Un Seo, Shin Kim, Jong-Wook Park, Dae Kyu Song, Hyun-Shik Lee, Sang Hyun Kim, Taeg Kyu Kwon
Cathepsin G is a serine protease secreted from activated neutrophils, it has important roles in inflammation and immune response. Moreover, cathepsin G promotes tumor cell-cell adhesion and migration in cancer cells. In this study, we investigated whether inhibition of cathepsin G could sensitize TRAIL-mediated apoptosis in cancer cells. An inhibitor of cathepsin G [Cathepsin G inhibitor I (Cat GI); CAS 429676-93-7] markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), lung cancer (A549) and cervical cancer (Hela) cells...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29277549/the-mtor-promotes-oxidative-stress-induced-apoptosis-of-mesangial-cells-in-diabetic-nephropathy
#9
Qian Lu, Yuexian Zhou, Meng Hao, Chengcheng Li, Jin Wang, Fanglin Shu, Lei Du, Xia Zhu, Qiaoli Zhang, Xiaoxing Yin
Glomerular mesangial cell (MC) apoptosis is one of the important mechanisms of glomerulosclerosis, which induces an increased severity of albuminuria and promotes the development of diabetic nephropathy (DN). However, the mechanism by which high glucose (HG) induces MCs apoptosis is not fully understood. In the present study, we investigated the effects of mTOR signalling on apoptosis in cultured MCs exposed to HG and in type I diabetes, and tried to clarify the specific mechanisms underlying these effects...
December 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29273760/urotensin-ii-induced-store-operated-ca2-entry-contributes-to-glomerular-mesangial-cell-proliferation-and-extracellular-matrix-protein-production-under-high-glucose-conditions
#10
Hitesh Soni, Adebowale Adebiyi
Glomerular mesangial cell (GMC) proliferation and matrix expansion are pathological hallmarks of a wide range of kidney diseases, including diabetic nephropathy. Although the circulating level of peptide hormone urotensin II (UII) and kidney tissue expression of UII and UII receptors (UTR) are increased in diabetic nephropathy, it remains unclear whether UII regulates GMC growth and extracellular matrix (ECM) accumulation. In this study, we tested the hypothesis that UII-induced Ca2+ signaling controls GMC proliferation and ECM production under normal and high glucose conditions...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29273684/sp600125-suppresses-keap1-expression-and-results-in-nrf2-mediated-prevention-of-diabetic-nephropathy
#11
Huan Zhang, Xiuxia Liu, Shanshan Zhou, Ye Jia, Ying Li, Yuguo Song, Junnan Wang, Hao Wu
c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125's protection against DN...
December 22, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29262395/salvianolic-acid-a-protects-against-diabetic-nephropathy-through-ameliorating-glomerular-endothelial-dysfunction-via-inhibiting-age-rage-signaling
#12
Biyu Hou, Guifen Qiang, Yuerong Zhao, Xiuying Yang, Xi Chen, Yu Yan, Xiaobo Wang, Chenge Liu, Li Zhang, Guanhua Du
BACKGROUND/AIMS: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. METHODS: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs...
December 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29259980/cyld-deubiquitinase-negatively-regulates-high-glucose-induced-nf-%C3%AE%C2%BAb-inflammatory-signaling-in-mesangial-cells
#13
Yanhui Li, Wei Huang, Youhua Xu, Luping Zhou, Yaling Liang, Chenlin Gao, Yang Long, Yong Xu
Nuclear factor-kappa B (NF-κB) is the key part of multiple signal transduction of inflammation in the pathogenesis of diabetic nephropathy (DN). The ubiquitin-proteasome system is extensively involved in the regulation of the NF-κB pathway. Cylindromatosis (CYLD) has deubiquitinase activity and acts as a negative regulator of the NF-κB signaling pathway. However, the association between CYLD and NF-κB inflammatory signaling in DN is unclear. In the present study, mouse glomerular mesangial cells (GMCs) and rat GMCs were stimulated by elevated concentrations of glucose (10, 20, and 30 mmol/L high glucose) or mannitol as the osmotic pressure control...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29248720/ckip-1-affects-the-polyubiquitination-of-nrf2-and-keap1-via-mediating-smurf1-to-resist-hg-induced-renal-fibrosis-in-gmcs-and-diabetic-mice-kidneys
#14
Wenyan Gong, Zhiquan Chen, Yezi Zou, Lei Zhang, Junying Huang, Peiqing Liu, Heqing Huang
Our previous study indicated that Casein kinase 2 interacting protein-1 (CKIP-1) could promote the activation of the nuclear factor E2-related factor 2 (Nrf2)/ antioxidant response element (ARE) pathway, playing a significant role in inhibiting the fibrosis of diabetic nephropathy (DN). However, the underlying mechanism is still unknown. Here, we investigated whether CKIP-1 affects the polyubiquitination of Nrf2 and its cytosolic inhibitor kelch like ECH-associated protein 1 (Keap1) via mediating Smad ubiquitylation regulatory factor-1 (Smurf1) to promote the activation of the Nrf2/ARE signaling and resist high glucose (HG)-induced renal fibrosis in glomerular mesangial cells (GMCs) and diabetic mice kidneys...
February 1, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29246323/triptolide-restores-autophagy-to-alleviate-diabetic-renal-fibrosis-through-the-mir-141-3p-pten-akt-mtor-pathway
#15
Xiao-Yu Li, Shan-Shan Wang, Zhe Han, Fei Han, Yun-Peng Chang, Yang Yang, Mei Xue, Bei Sun, Li-Ming Chen
Fibrosis is the major pathological feature of diabetic kidney disease (DKD). Autophagy, a process to maintain metabolic homeostasis, is obviously inhibited in DKD. Triptolide (TP) is a traditional Chinese medicine extract known for immune suppression and anti-inflammatory and anti-cancer activities. In this study, we investigated the effects of TP on autophagy and fibrosis in DKD. TP restored autophagy and alleviated fibrosis in DKD rats and high-glucose-incubated human mesangial cells. After we applied 3-methyladenine (an autophagy inhibitor) and autophagy-related gene 5-small interfering RNA (siRNA), we found that the improvement of fibrosis on TP was related to the restoration of autophagy...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29243784/value-of-immunofluorescence-mediated-detection-of-ig-c1q-c3-and-fra-for-the-identification-and-diagnosis-of-atypical-membranous-nephropathy
#16
W-X Wang, C-Y Hu
OBJECTIVE: The present study was to investigate the value of immunofluorescence-mediated detection of Ig, C1q, C3, and FRA for the identification and diagnosis of atypical membranous nephropathy (AMN). PATIENTS AND METHODS: Fifty-five patients with AMN and 135 patients with idiopathic membranous nephropathy (IMN) diagnosed by renal biopsy in our hospital were consecutively selected. The positive expressions of Ig, C1q, C3, and FRA by immunofluorescence were analyzed...
December 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29241070/protocatechuic-acid-ameliorates-high-glucose-induced-extracellular-matrix-accumulation-in-diabetic-nephropathy
#17
Yali Ma, Fang Chen, Suxia Yang, Baoping Chen, Jun Shi
Protocatechuic acid (PCA), a phenolic compound of anthocyanins, was reported to possess various pharmacologic properties, including anti-oxidant, anti-inflammatory, anti-apoptosis, anti-diabetic and anti-tumor activities. However, the role of PCA in diabetic nephropathy remains elusive. The present study was conducted to evaluate the effects of PCA on extracellular matrix (ECM) accumulation in high glucose (HG)-induced human mesangial cells (MCs) and explore the possible mechanism. Our results demonstrated that PCA obviously inhibited HG-induced proliferation of MCs in a dose-dependent manner...
December 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29229684/c-peptide-prevents-nf-%C3%AE%C2%BAb-from-recruiting-p300-and-binding-to-the-inos-promoter-in-diabetic-nephropathy
#18
Yanning Li, Xiaoping Li, Kunyu He, Bin Li, Kun Liu, Jinsheng Qi, Hui Wang, Yu Wang, Weigang Luo
C-peptide (CP) has demonstrated unique beneficial effects in diabetic nephropathy (DN), but whether and how CP regulates NF-κB and its coactivator, p300, to suppress inducible iNOS and antagonize DN are unknown. iNOS expression, NF-κB nuclear translocation, colocalization and binding of NF-κB to p300, binding of NF-κB to the inos promoter, and the bound NF-κB, p300, and histone 3 lysine 9 acetylation (H3K9ac) at binding sites were measured in high glucose-stimulated mesangial cells. We evaluated pathologic changes, iNOS expression, NF-κB, and p300 contents in diabetic rats...
December 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29229234/trans-resveratrol-mitigates-type-1-diabetes-induced-oxidative-dna-damage-and-accumulation-of-advanced-glycation-end-products-in-glomeruli-and-tubules-of-rat-kidneys
#19
Heba Al-Hussaini, Narayana Kilarkaje
Hyperglycemia induces the formation of advanced glycation end products (AGEs) and their receptors (RAGEs), which alter several intracellular signaling mechanisms leading to the onset and progression of diabetic nephropathy. The present study focused on, i) modulatory effects of trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) on structural changes, AGE (NƐ-carboxymethyl-lysine), RAGE, oxidative stress and DNA damage, and apoptosis, and ii) localization of fibrotic changes, AGE, RAGE, 8-oxo-dG and 4-hydroxynonenal (4-HNE) in diabetic rat kidneys...
December 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29224013/response-of-renal-podocytes-to-excessive-hydrostatic-pressure-a-pathophysiologic-cascade-in-a-malignant-hypertension-model
#20
Ramzia Abu Hamad, Sylvia Berman, Yafit Hachmo, Moshe Stark, Fadia Hasan, Keren Doenyas-Barak, Shai Efrati
BACKGROUND/AIMS: Renal injuries induced by increased intra-glomerular pressure coincide with podocyte detachment from the glomerular basement membrane (GBM). In previous studies, it was demonstrated that mesangial cells have a crucial role in the pathogenesis of malignant hypertension. However, the exact pathophysiological cascade responsible for podocyte detachment and its relationship with mesangial cells has not been fully elucidated yet and this was the aim of the current study. METHODS: Rat renal mesangial or podocytes were exposed to high hydrostatic pressure in an in-vitro model of malignant hypertension...
December 7, 2017: Kidney & Blood Pressure Research
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