SIRT1 reduction causes renal and retinal injury in diabetes through endothelin 1 and transforming growth factor β1

Journal of Cellular and Molecular Medicine
Rokhsana MortuzaSubrata Chakrabarti

Abstract

In diabetes, hyperglycaemia causes up-regulation of endothelin 1 (ET-1) and transforming growth factor beta 1 (TGF-β1). Previously we showed glucose reduces sirtuin1 (SIRT1), a class III histone deacetylase. Here, we investigated the regulatory role of SIRT1 on ET-1 and TGF-β1 expression. Human microvascular endothelial cells were examined following incubation with 25 mmol/l glucose (HG) and 5 mmol/l glucose (NG) with or without SIRT1 or histone acetylase p300 overexpression or knockdown. mRNA expressions of ET-1, TGF-β1, SIRT1, p300 and collagen 1α(I) were examined. SIRT1 enzyme activity, ET-1 and TGF-β1 protein levels were measured. Histone acetylation and endothelial permeability were further investigated. Similar analyses were performed in the kidneys and retinas of SIRT1 overexpressing transgenic mice with or without streptozotocin induced diabetes. Renal functions were evaluated. In the endothelial cells (ECs), HG caused increased permeability and escalated production of ET-1, TGF-β1, collagen Iα(I). These cells also showed increased p300 expression, histone acetylation and reduced SIRT1 levels. These changes were rectified in the ECs following p300 silencing or by SIRT1 overexpression, whereas SIRT1 knockdown or p300 ove...Continue Reading

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Citations

Dec 19, 2017·Frontiers in Aging Neuroscience·Hongdou LuoXu Zhang
Nov 20, 2018·Investigative Ophthalmology & Visual Science·Yong LinDongsheng Yan
Nov 5, 2019·Hypertension·Matthias Barton, Masashi Yanagisawa
Feb 2, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wanning WangLu Cai
Jul 24, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Sharifa AlzahraniNehal M Elsherbiny
Apr 20, 2018·Frontiers in Cardiovascular Medicine·Saumik BiswasSubrata Chakrabarti
Sep 19, 2019·Journal of Cellular Physiology·Nidhi KumariSenthil Kumar Ganesan
Nov 11, 2015·Journal of Translational Medicine·Ling ZhouMing-Jun Wang
Nov 1, 2017·Frontiers in Endocrinology·Madhu KhullarSatish K Raut
Mar 1, 2019·Endocrinology, Diabetes & Metabolism·Andrew Devon GordonSubrata Chakrabarti
Apr 26, 2018·International Journal of Molecular Medicine·Mengwen ZhouHuiming Zhang
Mar 19, 2019·Oxidative Medicine and Cellular Longevity·Shashank ShrishrimalRebecca E Oberley-Deegan
Feb 2, 2021·Frontiers in Pharmacology·Carlamaria ZojaDaniela Macconi
Mar 6, 2021·Molecular Therapy. Nucleic Acids·Xi YangYonghong Li
Feb 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Junying LuShu Nie
Mar 17, 2018·Progress in Retinal and Eye Research·Ximena Corso-DíazAnand Swaroop
May 18, 2021·Frontiers in Cell and Developmental Biology·Zhi FangQing R Miao
Jun 22, 2021·Frontiers in Endocrinology·Abdelrahim AlqudahLana McClements
Aug 12, 2021·Archives of Physiology and Biochemistry·Ainaz MihanfarMaryam Majidinia
Aug 10, 2021·Frontiers in Medicine·Jing XuDaisuke Koya

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Methods Mentioned

BETA
protein assay
transfection
ELISA
ELISAs
Assay
transfections
acetylation
histone acetylation
genotyping
transgenic

Software Mentioned

PASW Statistics

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