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https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#1
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca 2+ concentration and the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29446059/the-novel-involvement-of-podocyte-autophagic-activity-in-the-pathogenesis-of-lupus-nephritis
#2
Juan Jin, Meiyu Ye, Li Zhao, Wenli Zou, Wei Shen, Hongjuan Zhang, Jianguang Gong, Qiang He
BACKGROUND: Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated...
February 15, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#3
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29361670/podocyte-specific-knockin-of-pten-protects-kidney-from-hyperglycemia
#4
Huizhen Wang, Ziwei Feng, Jianteng Xie, Feng Wen, Menglei Jv, Tiantian Liang, Jing Li, Yanhui Wang, Yangyang Zuo, Sheng Li, Ruizhao Li, Zhilian Li, Bin Zhang, Xinling Liang, Shuangxin Liu, Wei Shi, Wenjian Wang
Aim Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been proved to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD). However, whether podocyte-specific knockin of PTEN protects the kidney against hyperglycemia in vivo remains undefined. Methods The inducible podocyte-specific PTEN knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop-loxP-PTEN mice with podocin-iCreERT2 mice...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29164562/resveratrol-transcriptionally-regulates-mirna-18a-5p-expression-ameliorating-diabetic-nephropathy-via-increasing-autophagy
#5
X-H Xu, D-F Ding, H-J Yong, C-L Dong, N You, X-L Ye, M-L Pan, J-H Ma, Q You, Y-B Lu
OBJECTIVE: To investigate the effects of resveratrol on autophagy in the chronically diabetic nephropathy and to study the effects of the different expression of microRNAs after resveratrol (RSV) treated in db/db mice (diabetic mice). MATERIALS AND METHODS: Db/m (non- diabetic) and db/db mice were randomly divided into intra gastric RSV treatment group or control group. Renal tissues were prepared for HE/PAS staining. In vitro, mouse podocytes cell lines were grown in different mediums with different dose of resveratrol treatment...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29155499/endoplasmic-reticulum-stress-induced-cell-death-in-podocytes
#6
REVIEW
Yu-Chi Cheng, Chien-An Chen, Hung-Chun Chen
Endoplasmic reticulum (ER) stress occurs in a variety of pathophysiological mechanisms, and there has been great interest in managing this pathway for the treatment of clinical diseases. Increased ER stress can block integrin-β1 glycosylation, decrease integrin-β1 protein expression and enhance cell death in podocytes. Autophagy is closely interconnected with ER stress to counteract the possible injurious effects related to the impairment of protein folding and is one of the intracellular protein degradation systems...
December 2017: Nephrology
https://www.readbyqxmd.com/read/29130363/antioxidant-role-of-autophagy-in-maintaining-the-integrity-of-glomerular-capillaries
#7
Jun Matsuda, Tomoko Namba, Yoshitsugu Takabatake, Tomonori Kimura, Atsushi Takahashi, Takeshi Yamamoto, Satoshi Minami, Shinsuke Sakai, Ryuta Fujimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Yoko Fukushima, Keiko Matsui, Tomoyoshi Soga, Yoshitaka Isaka
Autophagy is a lysosomal degradation system by which cytosolic materials and damaged organelles are broken down into basic components. To explore the physiological role of autophagy in glomerular endothelial cells (GEnCs), we compared the autophagic flux among cells in the kidney under starvation. Inhibition of autophagy by chloroquine administration significantly increased the number of autophagosomes or autolysosomes in GEnCs and proximal tubular cells, but not in podocytes, suggesting that the GEnCs exhibit substantial autophagic activity...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29070572/glucagon-like-peptide-1-analog-prevents-obesity-related-glomerulopathy-by-inhibiting-excessive-autophagy-in-podocytes
#8
HongLei Guo, Bin Wang, HongMei Li, LiLu Ling, Jianying Niu, Yong Gu
AIM: To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high fat diet-induced obesity-related glomerulopathy (ORG). METHODS: Male C57BL/6 mice fed a high fat diet for 12 weeks were treated with GLP-1 (200 μg/kg) or 0.9% saline for 4 weeks. Fasting blood glucose and insulin and the expression of podocin, nephrin, phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed...
October 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28987240/protein-tyrosine-phosphatase-1b-deficiency-in-podocytes-mitigates-hyperglycemia-induced-renal-injury
#9
Yoshihiro Ito, Ming-Fo Hsu, Ahmed Bettaieb, Shinichiro Koike, Aline Mello, Miguel Calvo-Rubio, Jose M Villalba, Fawaz G Haj
OBJECTIVE: Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. METHODS: To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO)...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28970584/endoplasmic-reticulum-stress-the-unfolded-protein-response-and-autophagy-in-kidney-diseases
#10
REVIEW
Andrey V Cybulsky
Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1α) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis...
November 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28916337/angiotensin-ii-induces-calcium-mediated-autophagy-in-podocytes-through-enhancing-reactive-oxygen-species-levels
#11
Na Gao, Hui Wang, Hongqiang Yin, Zhuo Yang
As well known, abnormalities of Angiotensin II (Ang II) is closely related with glomerular damage. This study was to investigate whether Ang II could affect autophagy in podocytes via oxidative stress, and whether autophagy had a positive role in protecting podocytes impaired by Ang II. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that Ang II induced podocyte death. The measurements of malondialdehyde (MDA) and H2O2 levels, and flow cytometry assay revealed that Ang II considerably increased reactive oxygen species (ROS) generation in podocytes...
November 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#12
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28837139/apelin-involved-in-progression-of-diabetic-nephropathy-by-inhibiting-autophagy-in-podocytes
#13
Yu Liu, Jia Zhang, Yangjia Wang, Xiangjun Zeng
Podocyte autophagy dysfunction has been reported to be responsible for the progression of diabetic nephropathy (DN), however, the factors contributed to autophagy dysfunction in type 2 diabetes are not fully understood. Among promoting factors in DN, an adipokine, apelin, had been showed to trigger podocyte dysfunction. Therefore, it is hypothesized that apelin, which is increased in plasma in type 2 diabetes, lead to podocyte apoptosis through inhibiting podocyte autophagy, which resulted in podocyte dysfunction followed by DN...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28819100/blockage-of-the-lysosome-dependent-autophagic-pathway-contributes-to-complement-membrane-attack-complex-induced-podocyte-injury-in-idiopathic-membranous-nephropathy
#14
Wei Jing Liu, Zhi-Hang Li, Xiao-Cui Chen, Xiao-Lu Zhao, Zhen Zhong, Chen Yang, Hong-Luan Wu, Ning An, Wei-Yan Li, Hua-Feng Liu
Dysregulation of autophagy-mediated podocyte homeostasis is proposed to play a role in idiopathic membranous nephropathy (IMN). In the present study, autophagic activity and lysosomal alterations were investigated in podocytes of IMN patients and in cultured podocytes exposed to sublytic terminal complement complex, C5b-9. C5b-9 upregulated the number of LC3 positive puncta and the expression of p62 in patient podocytes and in C5b-9 injuried podocyte model. The lysosomal turnover of LC3-II was not influenced, although the BECN1 expression level was upregulated after exposure of podocytes to C5b-9...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#15
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28761152/astragaloside-iv-protects-against-podocyte-injury-via-serca2-dependent-er-stress-reduction-and-ampk%C3%AE-regulated-autophagy-induction-in-streptozotocin-induced-diabetic-nephropathy
#16
Hengjiang Guo, Yi Wang, Xuemei Zhang, Yingjun Zang, Yang Zhang, Li Wang, Hao Wang, Yunman Wang, Aili Cao, Wen Peng
Aberrant endoplasmic reticulum (ER) stress and autophagy are associated with diabetic nephropathy. Here we investigated the effect of astragaloside IV (AS-IV) on the progression of diabetic nephropathy (DN) and the underlying mechanism involving ER stress and autophagy in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-incubated podocytes. The diabetic mice developed progressive albuminuria and glomerulosclerosis within 8 weeks, which were significantly ameliorated by AS-IV treatment in a dose-dependent manner...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757338/soluble-epoxide-hydrolase-in-podocytes-is-a-significant-contributor-to-renal-function-under-hyperglycemia
#17
Ahmed Bettaieb, Shinichiro Koike, Ming-Fo Hsu, Yoshihiro Ito, Samah Chahed, Santana Bachaalany, Artiom Gruzdev, Miguel Calvo-Rubio, Kin Sing Stephen Lee, Bora Inceoglu, John D Imig, Jose M Villalba, Darryl C Zeldin, Bruce D Hammock, Fawaz G Haj
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of renal failure, and podocyte dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose inhibition has beneficial effects on renal function. The aim of this study is to investigate the contribution of sEH in podocytes to hyperglycemia-induced renal injury. MATERIALS AND METHODS: Mice with podocyte-specific sEH disruption (pod-sEHKO) were generated, and alterations in kidney function were determined under normoglycemia, and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia...
November 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28729036/molecular-mechanisms-of-renal-aging
#18
REVIEW
Roland Schmitt, Anette Melk
Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons...
September 2017: Kidney International
https://www.readbyqxmd.com/read/28600173/autophagy-upregulation-ameliorates-cell-injury-in-sequestosome-1-knockout-podocytes-in%C3%A2-vitro
#19
Zhaoping Li, Yuan Yuan, Yan Meng, Ying Rong, Hao Bai, Liyong Chen
Autophagy is a catabolic process to maintain intracellular homeostasis that degrades damaged proteins and organelles in mammalian cells. 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 cell injury in human podocytes and the protective role of autophagy in this process. Here we show that the autophagy activity was decreased under the high glucose conditions and 72 h of high glucose exposure inhibited the cell viablity and aggravated cell injury...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28593583/regulating-autophagy-as-a-therapeutic-target-for-diabetic-nephropathy
#20
REVIEW
Munehiro Kitada, Yoshio Ogura, Itaru Monno, Daisuke Koya
PURPOSE OF REVIEW: Autophagy promotes cellular health in response to various cellular stresses and to changes in nutrient conditions. In this review, we focus on the role of autophagy in the pathogenesis of diabetic nephropathy and discuss the regulation of autophagy as a new therapeutic target for the suppression of diabetic nephropathy. RECENT FINDINGS: Previous studies have indicated that autophagy deficiency or insufficiency in renal cells, including podocytes, mesangial cells, endothelial cells and tubular cells, contributes to the pathogenesis of diabetic nephropathy...
July 2017: Current Diabetes Reports
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