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autophagy podocyte

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...
August 31, 2016: International Urology and Nephrology
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...
August 12, 2016: Biochimica et Biophysica Acta
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
Xiaochen Zhang, Hongqiang Yin, Zhigui Li, Tao Zhang, Zhuo Yang
Autophagy is a cellular pathway involved in degradation of damaged organelles and proteins in order to keep cellular homeostasis. It plays vital role in podocytes. Titanium dioxide nanoparticles (nano-TiO2) are known to induce autophagy in cells, but little has been reported about the mechanism of this process in podocytes and the role of autophagy in podocyte death. In the present study, we examined how nano-TiO2 induced authophagy. Besides that, whether autophagy could protect podocytes from the damage induced by nano-TiO2 and its mechanism was also investigated...
July 18, 2016: Cell Biology and Toxicology
Nan Mao, Rui-Zhi Tan, Shao-Qing Wang, Cong Wei, Xin-Li Shi, Jun-Ming Fan, Li Wang
Recent researches have reported the extensive pharmacological activities of Ginsenoside Rg1 including antioxidant, anti-inflammatory, and anticancer properties. Furthermore Rg1 was also shown to protect various kinds of cells from self-digestion by its anti-autophagy activity. In previous studies, angiotensin II (Ang II), a key mediator of renin-angiotensin system, has been demonstrated to contribute to the progression of renal injury including abnormal autophagy. However, whether Rg1 can relieve Ang II-induced autophagy in podocyte as well as the underlying molecular mechanism remains to be elucidated...
August 2016: Cell Biology International
Bin Wang, Wei Ding, Minmin Zhang, Hongmei Li, Honglei Guo, Lilu Lin, Jing Chen, Yong Gu
This study was undertaken to elucidate whether and how autophagy was regulated in aldosterone (Aldo)-induced podocyte injury and to examine its role in this model both in vitro and in vivo. In cultured podocytes, Aldo increased autophagy flux as indicated by the enhanced expression of LC3-II/LC3-I and the reduction of p62. Autophagy induction with rapamycin (RP) provided a cytoprotective effect, and inhibition of autophagy with Atg7-specific siRNA, chloroquine (CQ) or 3-methyladenine (3-MA) worsened Aldo-induced podocyte injury by attenuating endoplasmic reticulum (ER) stress...
May 26, 2016: Oncotarget
Hanan Elimam, Joan Papillon, Daniel R Kaufman, Julie Guillemette, Lamine Aoudjit, Richard W Gross, Tomoko Takano, Andrey V Cybulsky
Glomerular visceral epithelial cells (podocytes) play a critical role in the maintenance of glomerular permselectivity. Podocyte injury, manifesting as proteinuria, is the cause of many glomerular diseases. We reported previously that calcium-independent phospholipase A2γ (iPLA2γ) is cytoprotective against complement-mediated glomerular epithelial cell injury. Studies in iPLA2γ KO mice have demonstrated an important role for iPLA2γ in mitochondrial lipid turnover, membrane structure, and metabolism. The aim of the present study was to employ iPLA2γ KO mice to better understand the role of iPLA2γ in normal glomerular and podocyte function as well as in glomerular injury...
July 8, 2016: Journal of Biological Chemistry
Xiaofan Tan, Yuanhan Chen, Xinling Liang, Chunping Yu, Yuxiong Lai, Li Zhang, Xingchen Zhao, Hong Zhang, Ting Lin, Ruizhao Li, Wei Shi
High-level autophagy has an important role in maintaining the stable state of podocytes. The present study explored the influence of lipopolysaccharide (LPS) on autophagic activity in podocytes and demonstrated its mechanistic involvement in LPS-induced injury. Conditionally immortalized podocytes were cultured in vitro and were treated with chloroquine (CQ), LPS, LPS+rapamycin or LPS+3‑methyladenine (3‑MA). The autophagic vesicles and endoplasmic reticulum were observed using transmission electron microscopy...
July 2016: Molecular Medicine Reports
Wei Miaomiao, Liu Chunhua, Zhang Xiaochen, Chen Xiaoniao, Lin Hongli, Yang Zhuo
Podocytes are the major sites of vascular endothelial growth factor (VEGF) production in kidneys. Over-expression of VEGF is involved in the pathogenesis of diabetic nephropathy (DN), and an emerging body of evidence suggests that autophagy plays an important role in DN. In this study, the effect of autophagy on over-expressed VEGF along with its underlying mechanism was investigated in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-induced podocytes. We found that diabetes caused podocyte foot process effacement and VEGF upregulation significantly...
June 21, 2016: Molecular BioSystems
Dong Li, Zhenyu Lu, Zhongwei Xu, Junya Ji, Zhenfeng Zheng, Shan Lin, Tiekun Yan
Mechanical stress which would cause deleterious adhesive effects on podocytes is considered a major contributor to the early progress of diabetic nephropathy (DN). Our previous study has shown that spironolactone could ameliorate podocytic adhesive capacity in diabetic rats. Autophagy has been reported to have a protective role against renal injury. The present study investigated the underlying mechanisms by which spironolactone reduced adhesive capacity damage in podocytes under mechanical stress, focusing on the involvement of autophagy...
August 2016: Bioscience Reports
Ying Xu, Qi Zhou, Wei Xin, Zhaoping Li, Liyong Chen, Qiang Wan
It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN). Here we used shRNA transfection to knockdown the insulin receptor (IR) gene in cultured human immortalized podocytes as an in vitro insulin resistant model. Autophagy related proteins LC3, Beclin, and p62 as well as nephrin, a podocyte injury marker, were assessed using western blot and immunofluorescence staining. Our results show that autophagy is suppressed when podocytes lose insulin sensitivity and that treatment of rapamycin, an mTOR specific inhibitor, could attenuate insulin resistance induced podocytes injury via autophagy activation...
2016: PeerJ
J Liu, Q X Li, X J Wang, C Zhang, Y Q Duan, Z Y Wang, Y Zhang, X Yu, N J Li, J P Sun, F Yi
β-Arrestins are multifunctional proteins originally identified as negative adaptors of G protein-coupled receptors (GPCRs). Emerging evidence has also indicated that β-arrestins can activate signaling pathways independent of GPCR activation. This study was to elucidate the role of β-arrestins in diabetic nephropathy (DN) and hypothesized that β-arrestins contribute to diabetic renal injury by mediating podocyte autophagic process. We first found that both β-arrestin-1 and β-arrestin-2 were upregulated in the kidney from streptozotocin-induced diabetic mice, diabetic db/db mice and kidney biopsies from diabetic patients...
2016: Cell Death & Disease
Irena Audzeyenka, Dorota Rogacka, Agnieszka Piwkowska, Michal Rychlowski, Joanna Beata Bierla, Elżbieta Czarnowska, Stefan Angielski, Maciej Jankowski
Autophagy is an intracellular defense mechanism responsible for the turnover of damaged or non-functional cellular constituents. This process provides cells with energy and essential compounds under unfavorable environmental conditions-such as oxidative stress and hyperglycemia, which are both observed in diabetes. The most common diabetes complication is diabetic nephropathy (DN), which can lead to renal failure. This condition often includes impaired podocyte function. Here we investigated autophagic activity in rat podocytes cultured with a high insulin concentration (300nM)...
June 2016: International Journal of Biochemistry & Cell Biology
Ai-Li Cao, Li Wang, Xia Chen, Yun-Man Wang, Heng-Jiang Guo, Shuang Chu, Cheng Liu, Xue-Mei Zhang, Wen Peng
Endoplasmic reticulum (ER) stress, resulting from the accumulation of misfolded and/or unfolded proteins in ER membranes, is involved in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to investigate the role of ER stress inhibitors ursodeoxycholic acid (UDCA) and 4-phenylbutyrate (4-PBA) in the treatment of DN in db/db mice. Findings have revealed that diabetic db/db mice were more hyperglycemic than their non-diabetic controls, and exhibited a marked increase in body weight, water intake, urine volume, fasting plasma glucose, systolic blood pressure, glucose and insulin tolerance...
June 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Weili Wang, Juan Cai, Sha Tang, Ying Zhang, Xuejing Gao, Lijiao Xie, Zhirong Mou, Yuzhang Wu, Li Wang, Jingbo Zhang
BACKGROUND/AIMS: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion...
2016: Kidney & Blood Pressure Research
Pierre-Louis Tharaux, Tobias B Huber
No abstract text is available yet for this article.
March 2016: Diabetes
Qianying Lv, Fengjie Yang, Kun Chen, Yu Zhang
Podocyte injury induced by sublytic complement attack is the main feature of membranous nephropathy (MN). This study aimed at investigating the impact of sublytic complement attack-related autophagy on podocyte injury in vitro. Here, we show that sublytic complement attack enhances MPC5 podocyte autophagy in vitro. Inhibition of autophagy by treatment with 3-methyladenine (3-MA) significantly increased sublytic complement attack-induced changes in the injury-related morphology, stress fiber, and podocyte apoptosis, but decreased the survival and adhesion of MPC5 podocytes...
February 15, 2016: Experimental Cell Research
Kanae Yamamoto-Nonaka, Masato Koike, Katsuhiko Asanuma, Miyuki Takagi, Juan Alejandro Oliva Trejo, Takuto Seki, Teruo Hidaka, Koichiro Ichimura, Tatsuo Sakai, Norihiro Tada, Takashi Ueno, Yasuo Uchiyama, Yasuhiko Tomino
Studies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte-specific CD-knockout mice that developed proteinuria at 5 months of age and ESRD by 20-22 months of age...
September 2016: Journal of the American Society of Nephrology: JASN
Mi Bai, Ruochen Che, Yue Zhang, Yanggang Yuan, Chunhua Zhu, Guixia Ding, Zhanjun Jia, Songming Huang, Aihua Zhang
Evidence has demonstrated that Aldosterone (Aldo) is involved in the development and progression of chronic kidney diseases (CKDs). The purpose of this study was to investigate the role of autophagy in Aldo-induced podocyte damage and the underlying mechanism. Mouse podocytes were treated with Aldo in the presence or absence of 3-methyladenine (3-MA) and NAC. Cell apoptosis was investigated by detecting Annexin V conjugates, apoptotic bodies, caspase-3 activity, and the alteration of podocyte protein nephrin...
January 13, 2016: American Journal of Physiology. Renal Physiology
Shinji Kume, Daisuke Koya
Diabetic nephropathy is a leading cause of end stage renal disease and its occurance is increasing worldwide. The most effective treatment strategy for the condition is intensive treatment to strictly control glycemia and blood pressure using renin-angiotensin system inhibitors. However, a fraction of patients still go on to reach end stage renal disease even under such intensive care. New therapeutic targets for diabetic nephropathy are, therefore, urgently needed. Autophagy is a major catabolic pathway by which mammalian cells degrade macromolecules and organelles to maintain intracellular homeostasis...
December 2015: Diabetes & Metabolism Journal
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