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Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes.

 D. K. Kim  ;  B. Y. Nam  ;  J. J. Li  ;  J. T. Park  ;  S. H. Lee  ;  D. H. Kim  ;  J. Y. Kim  ;  H. Y. Kang  ;  S. H. Han  ;  T. H. Yoo  ;  D. S. Han  ;  S. W. Kang 
 DIABETOLOGIA, Vol.55(4) : 1205-1217, 2012 
Journal Title
Issue Date
Animals ; Biomarkers, Tumor/metabolism* ; Cell Enlargement* ; Cyclin-Dependent Kinases/metabolism ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/metabolism* ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/metabolism* ; Diabetic Nephropathies/pathology ; Gene Silencing ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Male ; Mechanistic Target of Rapamycin Complex 1 ; Mice ; Microfilament Proteins/metabolism ; Multiprotein Complexes ; Podocytes/metabolism ; Podocytes/pathology* ; Proteins/metabolism ; TOR Serine-Threonine Kinases
Diabetic nephropathy ; Hypertrophy ; Mouse ; mTOR complex 1 ; Podocyte ; TCTP
AIMS/HYPOTHESIS: Translationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes-induced podocyte hypertrophy. METHODS: We investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro. RESULTS: Glomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs. CONCLUSIONS/INTERPRETATION: These findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kang, Hye Young(강혜영)
Nam, Bo Young(남보영)
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Sun Ha(이순하)
Han, Dae Suk(한대석)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
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