Mitochondrial DNA Changes in Blood and Urine Display a Specific Signature in Relation to Inflammation in Normoalbuminuric Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Autor: Petrica L; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Center for Translational Research and Systems Medicine, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Vlad A; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania.; Department of Internal Medicine II, Division of Diabetes and Metabolic Diseases, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania., Gadalean F; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Muntean DM; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Center for Translational Research and Systems Medicine, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Functional Sciences III, Division of Pathophysiology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania., Vlad D; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania.; Department of Biochemistry and Pharmacology IV, Division of Pharmacology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania., Dumitrascu V; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania.; Department of Biochemistry and Pharmacology IV, Division of Pharmacology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania., Bob F; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Milas O; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Suteanu-Simulescu A; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Glavan M; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Jianu DC; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania.; Department of Neurosciences VIII, Division of Neurology I, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania., Ursoniu S; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Center for Translational Research and Systems Medicine, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania.; Department of Functional Sciences III, Division of Public Health and Health and History of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania., Balint L; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Mogos-Stefan M; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Ienciu S; Department of Internal Medicine II, Division of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania., Cretu OM; Department of Surgery I, Division of Surgical Semiology I, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; Emergency Clinical Municipal Hospital Timisoara, 300041 Timisoara, Romania., Popescu R; Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.; County Emergency Hospital Timisoara, 300723 Timisoara, Romania.; Department of Microscopic Morphology II, Division of Cell and Molecular Biology II, 'Victor Babes' University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Jun 06; Vol. 24 (12). Date of Electronic Publication: 2023 Jun 06.
DOI: 10.3390/ijms24129803
Abstrakt: Mitochondrial dysfunction is an important mechanism contributing to the development and progression of diabetic kidney disease (DKD). Mitochondrial DNA (mtDNA) levels in blood and urine were evaluated in relation to podocyte injury and proximal tubule (PT) dysfunction, as well as to a specific inflammatory response in normoalbuminuric DKD. A total of 150 type 2 diabetes mellitus (DM) patients (52 normoalbuminuric, 48 microalbuminuric, and 50 macroalbuminuric ones, respectively) and 30 healthy controls were assessed concerning the urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin and podocalyxin), PT dysfunction (kidney injury molecule-1 (KIM-1) and N -acetyl-β-(D)-glucosaminidase (NAG)), and inflammation (serum and urinary interleukins (IL-17A, IL-18, and IL-10)). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine via qRT-PCR. MtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies via analysis of the CYTB/B2M and ND2/B2M ratio. Multivariable regression analysis provided models in which serum mtDNA directly correlated with IL-10 and indirectly correlated with UACR, IL-17A, and KIM-1 (R 2 = 0.626; p < 0.0001). Urinary mtDNA directly correlated with UACR, podocalyxin, IL-18, and NAG, and negatively correlated with eGFR and IL-10 (R 2 = 0.631; p < 0.0001). Mitochondrial DNA changes in serum and urine display a specific signature in relation to inflammation both at the podocyte and tubular levels in normoalbuminuric type 2 DM patients.
Databáze: MEDLINE
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