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Han Xu, Na Guan, Ya-Li Ren, Qi-Jiao Wei, Ying-Hong Tao, Guo-Sheng Yang, Xiao-Ya Liu, Ding-Fang Bu, Ying Zhang, Sai-Nan Zhu
BACKGROUND: The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP3 R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection...
June 15, 2018: BMC Nephrology
Jiping Sun, Jing Lv, Wenjing Zhang, Lili Li, Jia Lv, Yingzhou Geng, Aiping Yin
This in vitro study was performed to identify the role of miR-124a in bone marrow stromal stem cells (BMSCs) therapy for H2 O2 -induced rat podocyte injury, and determine whether combination treatment with miR-124a could improve the protective effect of BMSCs. Cell viability of podocytes was detected by CCK-8 assay. Detection of ROS level, apoptotic rate, and autophagy rate was carried out using flow cytometry assays. Oxidative stress parameters were analyzed using the ELISA assays. MiR-124a and mRNA levels were determined using real-time PCR...
June 15, 2018: Journal of Cellular Biochemistry
Shu Yang, Mengyang Liu, Yuanli Chen, Chuanrui Ma, Lipei Liu, Buchang Zhao, Yong Wang, Xiaoju Li, Yan Zhu, Xiumei Gao, Deling Kong, Yajun Duan, Jihong Han, Xiaoxiao Yang
NaoXinTong Capsule (NXT), a Chinese medicine, is currently used to treat patients with cardiovascular and cerebrovascular diseases. Clinical observations indicate its anti-diabetic functions with unclear mechanisms. Herein, we report the effect of NXT on diabetic nephropathy (DN). Type 2 diabetic db/db mice were treated with NXT for 14 weeks. In the course of treatment, NXT reduced diabetes-increased glucose levels and improved renal functions. At the end of treatment, we found that NXT ameliorated serum lipid profiles and other biochemical parameters...
June 14, 2018: Scientific Reports
Emmanuel Ademola Anigilaje
BACKGROUND: Although urinary tract infection (UTI) resolves with prompt treatment in a majority of children, some children, especially those aged less than 5 years, also develop renal parenchymal scarring (RPS). RPS causes high blood pressure that may lead to severe chronic kidney disease and end-stage renal disease (ESRD). Although the risk of UTI is higher in white children than in black children, it is unknown whether RPS is more common in white children than in black children as data are scarce in this regard...
June 14, 2018: JMIR Research Protocols
Seung Seok Han, Mi-Yeon Yu, Kyung Don Yoo, Jung Pyo Lee, Dong Ki Kim, Yon Su Kim, Seung Hee Yang
Krüppel‑like factor 15 (KLF15), also known as kidney‑enriched transcription factor, is known to participate in podocyte differentiation. However, the role of KLF15 in chronic podocyte injury remains incompletely understood, particularly in proteinuric disease models. In the present study, the 5/6 nephrectomy mouse model was used to induce chronic podocyte injury. Human primary podocytes were isolated by flow cytometry and cultured to emulate the injury process in an in vitro system. Biopsied kidney tissue samples were obtained from patients with primary membranous nephropathy or diabetic nephropathy in order to analyze the relationship between glomerular KLF15 expression and subsequent outcomes...
June 11, 2018: International Journal of Molecular Medicine
Jinfeng Li, Bing Wang, Guangjie Zhou, Xiujuan Yan, Yuan Zhang
BACKGROUND: Tetrahydroxy stilbene glucoside (TSG) is an active ingredient of Heshouwu and is an antioxidant. The underlying mechanisms of the renoprotective effect of TSG in diabetic nephropathy have not been previously reported. In this study, we investigated the mechanisms of TSG in preventing podocytes injury in high glucose (HG) condition. METHODS: Cultured mouse podocytes (MPC5) were incubated in HG (30mmol/L) plus various concentration of TSG (0.1, 1 and 10μM) for 48 hours...
June 2018: American Journal of the Medical Sciences
Huihui Yang, Quan E Kan, Yong Su, Hua Man
It's known that long non-coding RNA CASC2 overexpression inhibit the JNK pathway in some disease models, while JNK pathway activation exacerbates diabetic nephropathy. Therefore we speculate that long non-coding RNA CASC2 can improve diabetic nephropathy by inhibiting JNK pathway. Thus, our study was carried out to investigate the involvement of CASC2 in diabetic nephropathy. We found that serum level of CASC2 was significantly lower in diabetic nephropathy patients than in normal people, and serum level of CASC2 showed no significant correlations with age, gender, alcohol consumption and smoking habits, but was correlated with course of disease...
June 11, 2018: Experimental and Clinical Endocrinology & Diabetes
Eliecer Coto, Carmen Díaz Corte, Salvador Tranche, Juan Gómez, Julián R Reguero, Belén Alonso, Sara Iglesias, Helena Gil-Peña, Xueqian Yin, Pablo Coto-Segura
The H19-IGF2 imprinted gene region could be implicated in the risk of developing impaired renal function (IRF). Our aim was to determine the association of several common H19-IGF2 variants and IRF in a cohort of elderly healthy individuals. The study involved 675 individuals >65 years of age, 184 with type 2 diabetes mellitus (T2DM), and 105 with IRF (estimated glomerular filtration rate [eGFR] <60). They were genotyped for two common H19 single nucleotide polymorphisms (SNPs) (rs2839698 and rs10732516), one H19-IGF2 intergenic indel (rs201858505), and one indel in the 3'UTR of the IGF2...
June 11, 2018: DNA and Cell Biology
Fateme Shamekhi Amiri
Subcellular organelles consist of smaller substructures called supramolecular assemblies and these in turn consist of macromolecules. Various subcellular organelles have critical functions that consist of genetic disorders of organelle biogenesis and several metabolic disturbances that occur during non-genetic diseases e.g. infection, intoxication and drug treatments. Mitochondrial damage can cause renal dysfunction as ischemic acute renal injury, chronic kidney disease progression. Moreover, mitochondrial dysfunction is an early event in aldosterone-induced podocyte injury and cardiovascular disease due to oxidative stress in chronic kidney disease...
June 7, 2018: Néphrologie & Thérapeutique
Sergi Clotet-Freixas, Maria Jose Soler, Vanesa Palau, Lidia Anguiano, Javier Gimeno, Ana Konvalinka, Julio Pascual, Marta Riera
Angiotensin-converting enzyme (ACE) and ACE2 play a critical role in the renin-angiotensin system (RAS) by altering angiotensin II (ANGII) levels, thus governing its deleterious effects. Both enzymes are altered by sex and diabetes, and play an important role in the development of diabetic nephropathy (DN). Importantly, previous evidence in diabetic and ACE2-deficient (ACE2KO) males suggest a sex-dependent crosstalk between renal ACE and ACE2. In the present work, we aimed to study the sex-specific susceptibility to diabetes and direct infusion of ANGII in kidney disease progression, with a special focus on its link to ACE2 and ACE...
June 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Amber M Cheatham, Shamara E Davis, Atanu K Khatua, Waldemar Popik
APOL1 risk alleles G1 or G2 are associated with a kidney disease phenotype exclusively in people of recent African ancestry. Here we show that exon 4 encoding a part of the APOL1 signal peptide is constitutively spliced in major APOL1 transcripts expressed in kidney glomerular and tubular cells. We demonstrate that constitutive splicing of exon 4 results from a suboptimal hnRNP A1 binding motif found in exon 4. Accordingly, a robust binding of hnRNP A1 protein to a consensus hnRNP A1 cis-acting element in exon 4 results in almost complete exclusion of exon 4 from the APOL1 minigene transcripts...
June 7, 2018: Scientific Reports
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Frances Tilley is the first author on 'Retromer associates with the cytoplasmic amino-terminus of polycystin-2', published in Journal of Cell Science. Frances conducted the work in this article while a PhD student in the lab of Peter Cullen at the University of Bristol, UK, but is now a postdoc in Corinne Antignac's lab at Imagine Institute, Paris, France, investigating the mechanisms of pathogenesis in Galloway-Mowat syndrome, with a focus on the role of podocytes on disease progression...
June 6, 2018: Journal of Cell Science
Mi Tian, Li Tang, Yuanyuan Wu, Srinivasan Beddhu, Yufeng Huang
Adiponectin (ApN) is a multifunctional adipokine. However high, rather than low, concentrations of ApN are unexpectedly found in patients with chronic kidney disease (CKD) via an as yet unknown mechanism and the role of ApN in CKD is unclear. We, herein, investigated the effect of ApN overexpression on the progressive renal injury resulted from deoxycorticosterone acetate-salt (DOCA) and angiotensin II (Ang-II) infusion using a transgenic, inducible ApN-overexpressing mouse model. Three groups of mice (wild type receiving no infusion (WT), WT and cyp1a1 ApN transgenic mice (ApN-Tg) receiving DOCA+Ang-II infusion (WT/DOCA+Ang-II and ApN-Tg/DOCA+Ang-II)) were assigned to receive a normal food containing 0...
June 6, 2018: American Journal of Physiology. Renal Physiology
Albert Yee, Joan Papillon, Julie Guillemette, Daniel R Kaufman, Chris R J Kennedy, Andrey V Cybulsky
Mutations in alpha-actinin-4 (actinin-4) result in hereditary focal segmental glomerulosclerosis (FSGS) in humans. Actinin-4 mutants induce podocyte injury due to dysregulation of the cytoskeleton and proteotoxicity. Injury may be associated with endoplasmic reticulum (ER) stress and polyubiquitination of proteins. We assessed if the chemical chaperone, 4-phenylbutyric acid (4-PBA) can ameliorate the proteotoxicity of an actinin-4 mutant. Actinin-4 K255E, which causes FSGS in humans (K256E in the mouse), showed enhanced ubiquitination, accelerated degradation, aggregate formation, and enhanced association with F-actin in glomerular epithelial cells (GECs)...
June 6, 2018: American Journal of Physiology. Renal Physiology
Katsue Suzuki-Inoue
Podoplanin is a type-I transmembrane sialomucin-like glycoprotein expressed on the surface of several kinds of tumor cells. The podoplanin receptor is a platelet activation receptor known as C-type lectin-like receptor 2 (CLEC-2), which has been identified as a receptor for the platelet-activating snake venom protein rhodocytin. CLEC-2 is highly expressed in platelets and megakaryocytes and expressed at lower levels in liver Kupffer cells. Podoplanin is expressed in certain types of tumor cells, including squamous cell carcinomas, seminomas, and brain tumors...
June 4, 2018: Platelets
W-J Liu, W-F Huang, L Ye, R-H Chen, C Yang, H-L Wu, Q-J Pan, H-F Liu
OBJECTIVE: Evidence suggested that deficiency of autophagy is involved in the pathogenesis of diabetic nephropathy (DN). However, some recent studies have also shown that autophagy is activated in renal cells under diabetic conditions. In this review, we discuss whether autophagy is inactivated in renal cells in DN as well as the therapeutic potential of autophagy for treating DN, in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information, original research articles and reviews, were gathered primarily through a search in PubMed and Cochrane database...
May 2018: European Review for Medical and Pharmacological Sciences
Wanbing Chen, You Wu, Gaofu Zhang, Mo Wang, Haiping Yang, Qiu Li
Primary nephrotic syndrome (PNS) is a devastating pediatric disorder. However, its mechanism remains unclear. Previous studies detected B7-1 in podocytes; meanwhile, γδ T cells play pivotal roles in immune diseases. Therefore, this study aimed to assess whether and how γδ T cells impact podocytes via the CD28/B7-1 pathway. WT and TCR δ -/- mice were assessed. LPS was used to induce nephropathy. Total γδ T and CD28+ γδ T cells were quantitated in mouse spleen and kidney samples. B7-1 and phosphor-SRC levels in the kidney were detected as well...
2018: BioMed Research International
N Gopalakrishnan, J Dhanapriya, C Padmakumar, T Dineshkumar, A A Kurien, R Sakthirajan, T Balasubramaniyan
Collapsing glomerulopathy (CG) is a distinct histopathologic pattern of glomerular injury characterized by global/segmental wrinkling of the glomerular basement membrane with podocyte hyperplasia and hypertrophy along with tubulointerstitial changes. There is no specific treatment for CG due to etiological heterogeneity, and newer insights into the pathogenesis may lead to the development of targeted therapy. The most common form of CG is the primary or idiopathic followed by secondary (due to viral infections, autoimmune disease, drugs, etc...
March 2018: Indian Journal of Nephrology
Filiz Mercantepe, Tolga Mercantepe, Atilla Topcu, Adnan Yılmaz, Levent Tumkaya
Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40 years has yet been discovered. This study investigated the effects of cisplatin on the kidney, the damage mechanism involved, and the potential capacity of agents such as amifostine, curcumin, and melatonin to elicit a future therapeutic protocol in cisplatin-induced nephrotoxicity at the ultrastructural and molecular levels. Our study consisted of five groups: control (saline solution only; group 1), cisplatin (cisplatin only; group 2), cisplatin + amifostine (group 3), cisplatin + curcumin (group 4), and cisplatin + melatonin (group 5)...
June 2, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Solange Moll, Yukari Yasui, Ahmed Abed, Takeshi Murata, Hideaki Shimada, Akira Maeda, Naoshi Fukushima, Masakazu Kanamori, Sabine Uhles, Laura Badi, Thomas Cagarelli, Ivan Formentini, Faye Drawnel, Guy Georges, Tobias Bergauer, Rodolfo Gasser, R Daniel Bonfil, Rafael Fridman, Hans Richter, Juergen Funk, Marcus J Moeller, Christos Chatziantoniou, Marco Prunotto
BACKGROUND: Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase extensively implicated in diseases such as cancer, atherosclerosis and fibrosis. Multiple preclinical studies, performed using either a gene deletion or a gene silencing approaches, have shown this receptor being a major driver target of fibrosis and glomerulosclerosis. METHODS: The present study investigated the role and relevance of DDR1 in human crescentic glomerulonephritis (GN)...
June 1, 2018: Journal of Translational Medicine
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