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https://www.readbyqxmd.com/read/28428331/a-personalized-model-of-coq2-nephropathy-rescued-by-the-wild-type-coq2-allele-or-dietary-coenzyme-q10-supplementation
#1
Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhanzheng Zhao, Patricio E Ray, Zhe Han
Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function...
April 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28428258/deletion-of-inositol-requiring-enzyme-1%C3%AE-in-podocytes-disrupts-glomerular-capillary-integrity-and-autophagy
#2
Daniel Robert Kaufman, Joan Papillon, Louise Larose, Takao Iwawaki, Andrey V Cybulsky
Inositol-requiring enzyme-1α (IRE1α) is an endoplasmic reticulum (ER)-transmembrane endoribonuclease-kinase, which plays an essential function in extraembryonic tissues during normal development, and is activated during ER stress. To address the functional role of IRE1α in glomerular podocytes, we produced podocyte-specific IRE1α deletion mice. In male mice, deletion of IRE1α in podocytes resulted in albuminuria beginning at 5 months of age, and worsening with time. Electron microscopy revealed focal podocyte foot process effacement in 9-month old male IRE1α deletion mice, as well as microvillous transformation of podocyte plasma membranes...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28427080/rapamycin-induces-autophagy-and-reduces-the-apoptosis-of-podocytes-under-a-stimulated-condition-of-immunoglobulin-a-nephropathy
#3
Shikai Liang, Juan Jin, Bo Lin, Jianguang Gong, Yiwen Li, Qiang He
Backgroud/Aims: The aim of this study was to investigate the potential renoprotective effect of rapamycin on the autophagy of podocytes treated with the supernatant of mesangial cells cultured with aggregated IgA1 (aIgA1) from immunoglobulin A nephropathy (IgAN) patients. METHODS: Monomeric IgA1 (mIgA1) was isolated from the serum of IgAN patients or healthy volunteers, and then transformed to aIgA1 by heating. Subsequently, the aIgA1-mesangial cell supernatant was prepared by collecting the medium of mouse mesangial cells (MSC1097) cultured with aIgA1 (100 mg/L) from different IgAN patients or healthy volunteers for 48 h...
April 18, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28424277/janus-kinase-2-regulates-transcription-factor-eb-expression-and-autophagy-completion-in-glomerular-podocytes
#4
Tamadher A Alghamdi, Syamantak Majumder, Karina Thieme, Sri N Batchu, Kathryn E White, Youan Liu, Angela S Brijmohan, Bridgit B Bowskill, Suzanne L Advani, Minna Woo, Andrew Advani
The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion...
April 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28404589/autophagy-is-activated-to-protect-against-podocyte-injury-in-adriamycin-induced-nephropathy
#5
Mixuan Yi, Lei Zhang, Yu Liu, Man J Livingston, Jian-Kang Chen, N Stanley Nahman, Fuyou Liu, Zheng Dong
Podocytes are highly differentiated epithelial cells wrapping glomerular capillary to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classical model of glomerular disease...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28391346/what-can-target-kidney-fibrosis
#6
Irina A Leaf, Jeremy S Duffield
Fibrosis, a characteristic of all chronic kidney diseases, is now recognized to be an independent predictor of disease progression. Deposition of pathological matrix in the walls of glomerular capillaries, the interstitial space and around arterioles both predicts and contributes to functional demise of the nephron and its surrounding vasculature. Recent identification of the major cell populations of fibroblast precursors in the kidney interstitium as pericytes and tissue-resident mesenchymal stem cells, and in the glomerulus as podocytes, parietal epithelial and mesangial cells, has enabled the study of the fibrogenic process in much greater depth directly in the fibroblast precursors...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28374806/resveratrol-protects-podocytes-against-apoptosis-via-stimulation-of-autophagy-in-a-mouse-model-of-diabetic-nephropathy
#7
Shan-Shan Huang, Da-Fa Ding, Sheng Chen, Cheng-Long Dong, Xiao-Long Ye, Yang-Gang Yuan, Ya-Min Feng, Na You, Jia-Rong Xu, Heng Miao, Qiang You, Xiang Lu, Yi-Bing Lu
Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28350056/notoginsenoside-r1-attenuates-glucose-induced-podocyte-injury-via-the-inhibition-of-apoptosis-and-the-activation-of-autophagy-through-the-pi3k-akt-mtor-signaling-pathway
#8
Guodong Huang, Bingyu Zou, Jianzhen Lv, Tongyu Li, Guoli Huai, Shaowei Xiang, Shilong Lu, Huan Luo, Yaping Zhang, Yi Jin, Yi Wang
Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins...
January 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28285376/association-of-podocyte-autophagosome-numbers-with-idiopathic-membranous-nephropathy-and-secondary-membranous-nephropathy
#9
Juan Jin, Huifang Zhan, Bo Lin, Yiwen Li, Wei Zhang, Qiang He
PURPOSE: This study was to investigate the relation between the number of autophagosomes in podocytes and the syndromes of idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (sMN). METHODS: The pathological changes in the kidney tissues of patients were detected with the hematoxylin and eosin staining, the periodic acid-Schiff reagent treatment, the Masson's trichrome staining and the immunofluorescence detection (IF). Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the IF assay pointing to LC3-II, an autophagic marker...
March 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28236091/viability-of-primary-cultured-podocytes-is-associated-with-extracellular-high-glucose-dependent-autophagy-downregulation
#10
Irena Audzeyenka, Dorota Rogacka, Agnieszka Piwkowska, Stefan Angielski, Maciej Jankowski
Structural and functional impairment of podocytes plays an important role in the development of diabetic nephropathy, a chronic complication of diabetes mellitus and leading cause of renal failure requiring renal replacement therapy. Autophagy plays a crucial role in podocyte viability and function, and its activity is modulated by a variety of pathophysiological factors found in diabetic milieu. Here we show that downregulation of autophagy is critical for podocyte survival in hyperglycemic environment. Moreover, long-term exposure to high glucose leads to inhibition of autophagy as well as to the development of insulin resistance in podocytes...
February 24, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28225005/autophagy-protects-against-palmitic-acid-induced-apoptosis-in-podocytes-in-vitro
#11
Xu-Shun Jiang, Xue-Mei Chen, Jiang-Min Wan, Hai-Bo Gui, Xiong-Zhong Ruan, Xiao-Gang Du
Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28158917/autophagy-is-involved-in-mouse-kidney-development-and-podocyte-differentiation-regulated-by-notch-signalling
#12
Chuyue Zhang, Wen Li, Junkai Wen, Zhuo Yang
Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation...
February 3, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28112381/notoginsenoside-r1-attenuates-glucose-induced-podocyte-injury-via-the-inhibition-of-apoptosis-and-the-activation-of-autophagy-through-the-pi3k-akt-mtor-signaling-pathway
#13
Guodong Huang, Bingyu Zou, Jianzhen Lv, Tongyu Li, Guoli Huai, Shaowei Xiang, Shilong Lu, Huan Luo, Yaping Zhang, Yi Jin, Yi Wang
Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28017719/repression-of-mir-217-protects-against-high-glucose-induced-podocyte-injury-and-insulin-resistance-by-restoring-pten-mediated-autophagy-pathway
#14
Juan Sun, Zhao Pin Li, Rui Qin Zhang, Hui Min Zhang
Podocyte damage is the initial hallmark of diabetic nephropathy (DN), leading to the increasing morbidity and mortality in diabetic patients. Recent researches have corroborated the critical roles of miRNAs in the pathological progression of DN. Here, elevation of miR-217 was verified in high glucose (HG)-stimulated podocytes. Moreover, blocking miR-217 expression antagonized HG-induced cell injury by attenuating the adverse role of HG on cell viability and inhibiting ROS levels and cell apoptosis. Simultaneously, miR-217 repression restored HG-disrupted insulin resistance by elevating glucose uptake and nephrin expression, an essential component for insulin-induced glucose uptake...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27887947/berberine-enhances-the-ampk-activation-and-autophagy-and-mitigates-high-glucose-induced-apoptosis-of-mouse-podocytes
#15
Yingli Jin, Shuping Liu, Qingshan Ma, Dong Xiao, Li Chen
High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27864431/apol1-mediated-cell-injury-involves-disruption-of-conserved-trafficking-processes
#16
Etty Kruzel-Davila, Revital Shemer, Ayala Ofir, Ira Bavli-Kertselli, Ilona Darlyuk-Saadon, Pazit Oren-Giladi, Walter G Wasser, Daniella Magen, Eid Zaknoun, Maya Schuldiner, Adi Salzberg, Daniel Kornitzer, Zvonimir Marelja, Matias Simons, Karl Skorecki
APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub-Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D...
April 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27816946/advanced-glycation-end-products-mediated-cellular-and-molecular-events-in-the-pathology-of-diabetic-nephropathy
#17
REVIEW
Anil Kumar Pasupulati, P Swathi Chitra, G Bhanuprakash Reddy
Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs)...
December 1, 2016: Biomolecular Concepts
https://www.readbyqxmd.com/read/27580730/how-many-podocyte-autophagosomes-are-there-in-immunoglobulin-a-nephropathy-and-idiopathic-membranous-nephropathy
#18
Shikai Liang, Juan Jin, Jianguang Gong, Bo Lin, Yiwen Li, Qiang He
PURPOSE: The aim of this study was to investigate the number of autophagosomes in podocyte from kidney tissue of immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN). METHODS: The changes in kidney tissue pathology were detected after hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome and immunofluorescence. The autophagosomes of podocyte were analyzed by transmission electron microscopy. Clinical data, including age, gender, edema, serum creatinine, estimated glomerular filtrating rate (eGFR), hematuria, urine protein excretion and serum albumin, were collected from inpatient medical record...
December 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27526674/hgf-alleviates-high-glucose-induced-injury-in-podocytes-by-gsk3%C3%AE-inhibition-and-autophagy-restoration
#19
Congying Zhang, Bo Hou, Siying Yu, Qi Chen, Nong Zhang, Hui Li
Podocyte injury or loss plays a major role in the pathogenesis of proteinuric kidney disease including diabetic nephropathy (DN). High basal level of autophagy is critical for podocyte health. Recent studies have revealed that hepatocyte growth factor (HGF) can ameliorate podocyte injury and proteinuria. However, little is known about the impact of HGF on podocyte autophagy. In this study, we investigated whether and how HGF affects autophagy in podocytes treated with high glucose (HG) conditions. HGF significantly diminishes apoptosis, oxidative stress and autophagy impairment inflicted by HG in podocytes...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27506738/autophagy-protects-human-podocytes-from-high-glucose-induced-injury-by-preventing-insulin-resistance
#20
Wei Xin, Zhaoping Li, Ying Xu, Yue Yu, Qi Zhou, Liyong Chen, Qiang Wan
OBJECTIVE: Insulin resistance is correlated with the progress of albuminuria in diabetic patients, and podocytes are crucial for maintaining the normal function of the glomerular filtration barrier. In the present study, we aimed to investigate the high glucose-induced insulin resistance and cell injury in human podocytes and the putative role of autophagy in this process. METHODS: Human podocytes were cultured in high glucose-supplemented medium and low glucose and high osmotic conditions were used for the controls...
September 2016: Metabolism: Clinical and Experimental
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