Maria Beatriz Monteiro1, Karina Thieme2, Daniele Pereira Santos-Bezerra3, Márcia Silva Queiroz4, Viktoria Woronik5, Marisa Passarelli6, Ubiratan Fabres Machado7, Daniel Giannella-Neto8, Maria Oliveira-Souza9, Maria Lúcia Corrêa-Giannella10. 1. Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #4305, 01246-903, São Paulo. Electronic address: maria.monteiro@usp.br. 2. Endocrine Division, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar 155, 05403-000, São Paulo. Electronic address: karina.thieme@usp.br. 3. Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #4305, 01246-903, São Paulo. Electronic address: dps.daniele@usp.br. 4. Lipids Laboratory (LIM-10), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #3305, 01246-903, São Paulo. Electronic address: marciasqz@gmail.com. 5. Laboratory of Renal Pathophysiology (LIM-16), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #3345, 01246-903, São Paulo. Electronic address: viktoriaw@usp.br. 6. Lipids Laboratory (LIM-10), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #3305, 01246-903, São Paulo. Electronic address: mpassere@usp.br. 7. Laboratory of Metabolism and Endocrinology, Department of Physiology and Biophysics, Biomedical Sciences Institute, Av. Prof. Lineu Prestes 1524 #126, 05508-000, São Paulo. Electronic address: ubiratan@icb.usp.br. 8. Programa de Pós-Graduação em Medicina, Universidade Nove de Julho - UNINOVE, R. Vergueiro, 235/249, 01504-001, São Paulo. Electronic address: dgiannella@terra.com.br. 9. Laboratory of Renal Physiology, Department of Physiology and Biophysics, Biomedical Sciences Institute, Av. Prof. Lineu Prestes 1524 #227, 05508-000, São Paulo. Electronic address: souza@icb.usp.br. 10. Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #4305, 01246-903, São Paulo; Laboratory of Cellular and Molecular Endocrinology (LIM-25), Cell and Molecular Therapy Center (NUCEL), University of São Paulo Medical School, R. Pangaré, 05360-120, São Paulo. Electronic address: malugia@lim25.fm.usp.br.
Abstract
PURPOSE: After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD. METHODS: qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. RESULTS: No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P=0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P=0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r=0.43; P=0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r=- 0.57; P=0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25mM glucose and to albumin. CONCLUSIONS: Β2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy.
PURPOSE: After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD. METHODS: qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in humanembryonic kidney epithelium-like (HEK-293) cells exposed to 25mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. RESULTS: No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P=0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P=0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r=0.43; P=0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r=- 0.57; P=0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25mM glucose and to albumin. CONCLUSIONS: Β2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy.
Authors: Paul Luchian Aldea; Andreea Liana Rachisan; Bogdan Ioan Stanciu; Andrei Picos; Alina Monica Picos; Dan Ioan Delean; Ramona Stroescu; Magdalena Iuliana Starcea; Cristina Maria Borzan; Florin Ioan Elec Journal: Front Pediatr Date: 2022-06-03 Impact factor: 3.569
Authors: Maria Beatriz Monteiro; Tatiana S Pelaes; Daniele P Santos-Bezerra; Karina Thieme; Antonio M Lerario; Sueli M Oba-Shinjo; Ubiratan F Machado; Marisa Passarelli; Suely K N Marie; Maria Lúcia Corrêa-Giannella Journal: Front Endocrinol (Lausanne) Date: 2020-04-30 Impact factor: 5.555