Agricultural and Biological Sciences, Biochemistry, Genetics and Molecular Biology, Clinical Biochemistry, Molecular Medicine
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Scopus Publications
Scopus Publications
MicroRNAs and vascular damage in chronic kidney disease: advances and clinical implications Regiane Stafim da Cunha, Carolina Amaral Bueno Azevedo, Guilherme Miniskiskosky, Paulo Cézar Gregório, Andréa Emilia Marques Stinghen Brazilian Journal of Nephrology, 2025 Chronic kidney disease (CKD) is closely associated with endothelial dysfunction and vascular calcification, which are major contributors to the development of cardiovascular disease in this population. MicroRNAs (miRNAs) are a group of non-coding RNAs that regulate gene expression and other cellular processes. Recent studies have demonstrated that changes in the levels of several miRNAs are associated with the progression of renal dysfunction. Patients with CKD have reduced levels of miR-126, a microRNA produced by the endothelium that has an atheroprotective function. Reduced miRNA levels that inhibit vascular calcification, such as miR-133a and miR-204-5p, are also found in patients with CKD. These changes may contribute to vascular dysfunction in these patients. Therefore, understanding the profile of microRNAs in the context of CKD may be important for the identification of new biomarkers and potential therapeutic targets. Given the growing relevance of microRNA analysis, this review addresses recent advances in the study of microRNAs related to vascular dysfunction in CKD and their potential applications in translational clinical practice.
The epigenetic of monoterpenes in the pathological context Advances in Genetics Research, 2024
The Role of α3β1 Integrin Modulation on Fabry Disease Podocyte Injury and Kidney Impairment Bruna Bosquetti, Aline Aparecida Santana, Paulo Cézar Gregório, Regiane Stafim da Cunha, Guilherme Miniskiskosky, et al. Toxins, 2023 Podocyte dysfunction plays a crucial role in renal injury and is identified as a key contributor to proteinuria in Fabry disease (FD), primarily impacting glomerular filtration function (GFF). The α3β1 integrins are important for podocyte adhesion to the glomerular basement membrane, and disturbances in these integrins can lead to podocyte injury. Therefore, this study aimed to assess the effects of chloroquine (CQ) on podocytes, as this drug can be used to obtain an in vitro condition analogous to the FD. Murine podocytes were employed in our experiments. The results revealed a dose-dependent reduction in cell viability. CQ at a sub-lethal concentration (1.0 µg/mL) induced lysosomal accumulation significantly (p < 0.0001). Morphological changes were evident through scanning electron microscopy and immunofluorescence, highlighting alterations in F-actin and nucleus morphology. No significant changes were observed in the gene expression of α3β1 integrins via RT-qPCR. Protein expression of α3 integrin was evaluated with Western Blotting and immunofluorescence, demonstrating its lower detection in podocytes exposed to CQ. Our findings propose a novel in vitro model for exploring secondary Fabry nephropathy, indicating a modulation of α3β1 integrin and morphological alterations in podocytes under the influence of CQ.
Renocardiac Effects of p-Cresyl Sulfate Administration in Acute Kidney Injury Induced by Unilateral Ischemia and Reperfusion Injury In Vivo Carlos Alexandre Falconi, Fernanda Fogaça-Ruiz, Jéssica Verônica da Silva, Raquel Silva Neres-Santos, Carmen Lucía Sanz, et al. Toxins, 2023 The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1β and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI.
Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy Paulo C. Gregório, Gilson Biagini, Regiane S. da Cunha, Júlia Budag, Ana Maria Martins, et al. Kidney and Blood Pressure Research, 2022 <b><i>Background and Aims:</i></b> Inflammation and endothelial damage play a pivotal role in Fabry disease (FD) manifestations. In daily clinical practice, FD is mainly monitored by traditional biomarkers of target organ injury, such as serum creatinine and proteinuria, which provide no information about inflammation and endothelial damage. <b><i>Materials and Methods:</i></b> We investigated the serum levels of 3-nitrotyrosine (3-NT), an oxidative stress biomarker, and of growth differentiation factor-15 (GDF-15) and syndecan-1 in classical FD patients on enzyme replacement therapy (ERT) for at least 6 months and their relationship with Fabry-related cardiac and renal manifestations. <b><i>Results:</i></b> Fifty-two classical FD patients (37 females) on ERT for 62.0 ± 27.5 months were included in the study. The main clinical manifestations included nephropathy (67.3%) and cardiomyopathy (21.1%). Serum levels of 3-NT, syndecan-1, and GDF-15 were 33.3 (4.8–111.1) nmol/mL, 55.7 (38.8–74.9) ng/mL, and 541.8 (392.2–784.4) pg/mL, respectively. There was a direct correlation between interventricular septal thickness and serum GDF-15 (<i>r</i> = 0.59; <i>p</i> &#x3c; 0.001) and syndecan-1 (<i>r</i> = 0.30, <i>p</i> = 0.04). Among kidney parameters, there was a significant correlation between estimated glomerular filtration rate and GDF-15 (<i>r</i> = −0.61; <i>p</i> &#x3c; 0.001), as well as between 24 h proteinuria and syndecan-1 (<i>r</i> = 0.28; <i>p</i> = 0.04). Serum GDF-15 levels were significantly higher in patients with cardiomyopathy (<i>p</i> = 0.03) as well in those with both nephropathy and cardiomyopathy (<i>p</i> = 0.02) than in patients without these comorbidities. Serum GDF-15 levels were also significantly higher in patients who started ERT at an older age (≥40 years). In multivariate analysis, syndecan-1, 3-NT, GDF-15, time on ERT, and arterial pressure differentiated Fabry patients with both cardiac and renal involvement from those without these manifestations. <b><i>Conclusions:</i></b> GDF-15 and syndecan-1 were associated with parameters of cardiac and renal involvement in classic FD patients on ERT. Their potential association with residual risk and disease outcomes should be investigated.
The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction Regiane Stafim da Cunha, Carolina Amaral Bueno Azevedo, Carlos Alexandre Falconi, Fernanda Fogaça Ruiz, Sophie Liabeuf, et al. Toxins, 2022 Uremic toxins are a heterogeneous group of molecules that accumulate in the body due to the progression of chronic kidney disease (CKD). These toxins are associated with kidney dysfunction and the development of comorbidities in patients with CKD, being only partially eliminated by dialysis therapies. Importantly, drugs used in clinical treatments may affect the levels of uremic toxins, their tissue disposition, and even their elimination through the interaction of both with proteins such as albumin and cell membrane transporters. In this context, protein-bound uremic toxins (PBUTs) are highlighted for their high affinity for albumin, the most abundant serum protein with multiple binding sites and an ability to interact with drugs. Membrane transporters mediate the cellular influx and efflux of various uremic toxins, which may also compete with drugs as substrates, and both may alter transporter activity or expression. Therefore, this review explores the interaction mechanisms between uremic toxins and albumin, as well as membrane transporters, considering their potential relationship with drugs used in clinical practice.
The intricate relationship between gut and kidney Regiane S. Cunha, Andréa E. M. Stinghen Jornal Brasileiro De Nefrologia Orgao Oficial De Sociedades Brasileira E Latino Americana De Nefrologia, 2018
Evaluation of uleine in cellular adhesion of murine melanoma (B16F-10) and human gastric carcinoma cells (KATO III and MKN) Latin American Journal of Pharmacy, 2013
Vascular calcification in chronic kidney disease: a review. Jornal Brasileiro De Nefrologia Orgao Oficial De Sociedades Brasileira E Latino Americana De Nefrologia, 2013
Characteristics and causes of immune dysfunction related to uremia and dialysis Peritoneal Dialysis International, 2008
Reply [6] R. Pecoits-Filho, S. Goncalves, A. E. Stinghen, M. C. Riella Nephrology Dialysis Transplantation, 2007
Factors contributing to the differences in peritonitis rates between centers and regions Peritoneal Dialysis International, 2007
Controlling inflammation in peritoneal dialysis: The role of PD-related factors as potential intervention targets Peritoneal Dialysis International, 2007
The recommendations from the International Society for Peritoneal Dialysis for Peritonitis Treatment: a single-center historical comparison. Advances in Peritoneal Dialysis Conference on Peritoneal Dialysis, 2004
