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PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy
by
Wang, Ziying
, Sun, Yu
, Tang, Wei
, Lu, Yi
, Fu, Yi
, Jia, Meng
, Zhang, Yan
, Zhou, Di
, Liu, Min
, Yi, Fan
, Wang, Xiaojie
, Zhou, Meng
in
13/109
/ 13/2
/ 13/31
/ 13/51
/ 14/19
/ 14/28
/ 38/77
/ 631/80/642/333
/ 631/80/82/39/2348
/ 64/60
/ 692/699/1585/2759/1419
/ 82/29
/ 82/81
/ 96/95
/ Acetylation
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Biopsy
/ Biosynthesis
/ Cell Biology
/ Cell Culture
/ Cell Death
/ Cytoprotection
/ Diabetes
/ Diabetes mellitus
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Experimental - pathology
/ Diabetic Nephropathies - metabolism
/ Diabetic Nephropathies - pathology
/ Diabetic nephropathy
/ Forkhead Box Protein O1 - metabolism
/ FOXO1 protein
/ Glucose - toxicity
/ Homeostasis
/ Humans
/ Immunology
/ Kidney - metabolism
/ Kidney - pathology
/ Kidneys
/ Life Sciences
/ Medical innovations
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - metabolism
/ Mitochondria - ultrastructure
/ Mitophagy
/ Nephropathy
/ Organelle Biogenesis
/ Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
/ Podocytes - metabolism
/ Podocytes - pathology
/ Podocytes - ultrastructure
/ Progranulins - deficiency
/ Progranulins - metabolism
/ Proteinuria
/ Rats
/ Rodents
/ SIRT1 protein
/ Sirtuin 1 - metabolism
2019
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PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy
by
Wang, Ziying
, Sun, Yu
, Tang, Wei
, Lu, Yi
, Fu, Yi
, Jia, Meng
, Zhang, Yan
, Zhou, Di
, Liu, Min
, Yi, Fan
, Wang, Xiaojie
, Zhou, Meng
in
13/109
/ 13/2
/ 13/31
/ 13/51
/ 14/19
/ 14/28
/ 38/77
/ 631/80/642/333
/ 631/80/82/39/2348
/ 64/60
/ 692/699/1585/2759/1419
/ 82/29
/ 82/81
/ 96/95
/ Acetylation
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Biopsy
/ Biosynthesis
/ Cell Biology
/ Cell Culture
/ Cell Death
/ Cytoprotection
/ Diabetes
/ Diabetes mellitus
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Experimental - pathology
/ Diabetic Nephropathies - metabolism
/ Diabetic Nephropathies - pathology
/ Diabetic nephropathy
/ Forkhead Box Protein O1 - metabolism
/ FOXO1 protein
/ Glucose - toxicity
/ Homeostasis
/ Humans
/ Immunology
/ Kidney - metabolism
/ Kidney - pathology
/ Kidneys
/ Life Sciences
/ Medical innovations
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - metabolism
/ Mitochondria - ultrastructure
/ Mitophagy
/ Nephropathy
/ Organelle Biogenesis
/ Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
/ Podocytes - metabolism
/ Podocytes - pathology
/ Podocytes - ultrastructure
/ Progranulins - deficiency
/ Progranulins - metabolism
/ Proteinuria
/ Rats
/ Rodents
/ SIRT1 protein
/ Sirtuin 1 - metabolism
2019
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PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy
by
Wang, Ziying
, Sun, Yu
, Tang, Wei
, Lu, Yi
, Fu, Yi
, Jia, Meng
, Zhang, Yan
, Zhou, Di
, Liu, Min
, Yi, Fan
, Wang, Xiaojie
, Zhou, Meng
in
13/109
/ 13/2
/ 13/31
/ 13/51
/ 14/19
/ 14/28
/ 38/77
/ 631/80/642/333
/ 631/80/82/39/2348
/ 64/60
/ 692/699/1585/2759/1419
/ 82/29
/ 82/81
/ 96/95
/ Acetylation
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Biopsy
/ Biosynthesis
/ Cell Biology
/ Cell Culture
/ Cell Death
/ Cytoprotection
/ Diabetes
/ Diabetes mellitus
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Experimental - pathology
/ Diabetic Nephropathies - metabolism
/ Diabetic Nephropathies - pathology
/ Diabetic nephropathy
/ Forkhead Box Protein O1 - metabolism
/ FOXO1 protein
/ Glucose - toxicity
/ Homeostasis
/ Humans
/ Immunology
/ Kidney - metabolism
/ Kidney - pathology
/ Kidneys
/ Life Sciences
/ Medical innovations
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - metabolism
/ Mitochondria - ultrastructure
/ Mitophagy
/ Nephropathy
/ Organelle Biogenesis
/ Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
/ Podocytes - metabolism
/ Podocytes - pathology
/ Podocytes - ultrastructure
/ Progranulins - deficiency
/ Progranulins - metabolism
/ Proteinuria
/ Rats
/ Rodents
/ SIRT1 protein
/ Sirtuin 1 - metabolism
2019
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PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy
Journal Article
PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy
2019
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Overview
Mitochondrial dysfunction is considered as a key mediator in the pathogenesis of diabetic nephropathy (DN). Therapeutic strategies targeting mitochondrial dysfunction hold considerable promise for the treatment of DN. In this study, we investigated the role of progranulin (PGRN), a secreted glycoprotein, in mediating mitochondrial homeostasis and its therapeutic potential in DN. We found that the level of PGRN was significantly reduced in the kidney from STZ-induced diabetic mice and patients with biopsy-proven DN compared with healthy controls. In DN model, PGRN-deficient mice aggravated podocyte injury and proteinuria versus wild-type mice. Functionally, PGRN deficiency exacerbated mitochondrial damage and dysfunction in podocytes from diabetic mice. In vitro, treatment with recombinant human PGRN (rPGRN) attenuated high glucose-induced mitochondrial dysfunction in podocytes accompanied by enhanced mitochondrial biogenesis and mitophagy. Inhibition of mitophagy disturbed the protective effects of PGRN in high glucose-induced podocytotoxicity. Mechanistically, we demonstrated that PGRN maintained mitochondrial homeostasis via PGRN-Sirt1-PGC-1α/FoxO1 signaling-mediated mitochondrial biogenesis and mitophagy. Finally, we provided direct evidence for therapeutic potential of PGRN in mice with DN. This study provides new insights into the novel role of PGRN in maintaining mitochondrial homeostasis, suggesting that PGRN may be an innovative therapeutic strategy for treating patients with DN.
Publisher
Nature Publishing Group UK,Springer Nature B.V
Subject
/ 13/2
/ 13/31
/ 13/51
/ 14/19
/ 14/28
/ 38/77
/ 64/60
/ 82/29
/ 82/81
/ 96/95
/ Animals
/ Biomedical and Life Sciences
/ Biopsy
/ Diabetes
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Experimental - pathology
/ Diabetic Nephropathies - metabolism
/ Diabetic Nephropathies - pathology
/ Forkhead Box Protein O1 - metabolism
/ Humans
/ Kidneys
/ Mitochondria - ultrastructure
/ Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
/ Rats
/ Rodents
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