Diogo Barros Peruchetti

Scopus Publications

Angiotensin-converting enzyme 2 enhances megalin-mediated albumin endocytosis in proximal tubule cells by restraining Angiotensin II/AT1R
Helena R. Peixoto, Rodrigo P. Silva‐Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Sarah A. S. Alves, et al.
Journal of Physiology, 2026
Proximal tubule epithelial cell (PTEC) albumin transport efficiently prevents albuminuria under physiological conditions. This process occurs through a receptor‐mediated endocytosis, being megalin, cubilin and amnionless the receptor complex involved. Evidence suggests that renin–angiotensin system (RAS) components regulate albumin transport in proximal tubules (PTs). However, the impact of angiotensin‐converting enzyme type 2 (ACE2) on this process remains uncertain. Overexpressing ACE2 in HEK‐293 promotes a selective increase in receptor‐mediated albumin endocytosis, without changes in fluid‐phase endocytosis. This effect was correlated with increased albumin cell surface binding and increased megalin expression. Treatment with ACE2 inhibitor MLN‐4760 blocked the increase in albumin endocytosis induced by ACE2 overexpression in an angiotensin II (Ang II) / AT1R dependent manner. These results were confirmed in LLC‐PK1 cells. Using a murine albumin overload model, we observed that proteinuria and reduced PT albumin reabsorption was correlated with lower ACE2 protein expression. Using RNA‐Seq databases, we verified that low ACE2 expression correlated with proteinuria in patients with kidney disease. Our results indicate that ACE2 decreases the Ang II/AT1R pathway and increases megalin expression, which in turn enhances PT albumin transport. This pathway is altered in experimental models and patients with kidney diseases. image Key points ACE2 overexpression increases PT albumin transport. ACE2 overexpression increases megalin expression. ACE2 increases albumin transport by decreasing Ang II / AT1R signalling. Akt activation mediates the increased albumin transport induced by ACE2. Decreased ACE2 expression correlates with proteinuria in mouse models and patients.
Losartan treatment attenuates the cardiorenal alterations in a rat model of hemorrhagic insular stroke
Liliane Ramos dos Santos Machado, Itamar Couto Guedes Jesus, Marcos Eliezeck, Ana Caroline Ventris de Godoy, Matheus Henrique da Silva Cruz, et al.
Clinical Autonomic Research, 2026
Mas-related G protein-coupled receptor type D deficiency promotes tubulointerstitial injury and fibrosis associated with proteinuria in male mice
Laura B. F. Oliveira, Arthur F. Iost, Lucas R. A. Ribeiro, Maria Aparecida R. Vieira, Thiago Verano‐Braga, et al.
Physiological Reports, 2026
Kidney diseases are non‐communicable, progressive diseases with high morbidity and mortality rates worldwide. A key feature of disease progression is the development of tubulointerstitial injury accompanied by proteinuria, a process mediated in part by dysregulation of the Renin‐Angiotensin System (RAS). Recently, a novel protective RAS axis consisting of alamandine (Ala) and its receptor, the Mas‐related G protein‐coupled receptor type D (MrgD), has been identified. While the Ala/MrgD pathway has been implicated in the cardiovascular regulation, its role in renal physiology remains unknown. In this study, we investigated whether basal MrgD deficiency affects the renal structure and function. Male 8‐12‐week‐old C57Bl6/J wild‐type (WT) and MrgD knockout (MrgD‐KO) mice were used. MrgD‐KO exhibited reduced water intake and urine output, increased tubular reabsorption of Na + and glucose, and marked proteinuria associated with increased fractional excretion of proteins. In addition, MrgD deficiency was associated with elevated urinary lactate dehydrogenase levels, increased urinary proteins: creatinine ratio, enhanced urinary γ‐glutamyltransferase activity, and the presence of tubulointerstitial injury and fibrosis in the renal cortex. Collectively, these findings demonstrate that basal MrgD deficiency promotes tubular dysfunction and injury, thereby expanding current understanding of the role of novel RAS peptides in kidney disease.
Short-term hypothyroidism impairs the daily oscillations of renal circadian clock and function in a sex-dependent manner
Derrick Kretli-Souza, Bruno Henrique Gomes, Letícia Selvatici-Tolentino, Yancka Oliveira-Damasceno, Ana Flávia Peixoto-Dias, et al.
American Journal of Physiology Renal Physiology, 2025
Hypothyroidism alters the kidney circadian clock machinery and renal function in a sex-dependent manner, potentially contributing to early-stage kidney dysfunction. Female rats exhibited more severe rhythmic impairments under hypothyroid conditions, including reduced creatinine clearance, increased protein and glucose loss in urine over 24 h, and disrupted circadian oscillations in renal clock components, indicating a greater susceptibility of females to hypothyroidism-induced metabolic disturbances associated with circadian disruption.
Effects of different sodium concentrations in fluids on brain, lung, and kidney in experimental ischemic stroke
Camila M. Bessa, Adriana L. Vilardo, Diogo B. Peruchetti, Pedro H. L. Conceição, Celso Caruso-Neves, et al.
Scientific Reports, 2025
Kidney dysfunction induced by a hyperpalatable diet: Role of sodium/glucose Co-transporter inhibition in male mice
Mariana Coelho Moraes, Laura Barroso Ferreira Oliveira, Mariana Rodrigues Campos, Paulo Francisco Reis Barahuna-Filho, Pablo Leal Cardozo, et al.
European Journal of Pharmacology, 2025
Transition between Healthy Aging and Renal Dysfunction during Natural Aging: Role of p21, p16, Nicotinamide Adenine Dinucleotide Phosphate Hydrogen Oxidase, Nuclear Factor-Kappa B, and Cyclooxygenase-2
Grazielle Caroline da Silva, Thiago Frederico Diniz, Rosária Dias Aires, Diogo Barros Peruchetti, Rafaela Fernandes da Silva, et al.
Gerontology, 2025
Introduction: Aging is a key risk factor for progressive kidney disease, yet the mechanisms underlying age-related renal dysfunction remain poorly understood. This study aimed to investigate the role of cyclooxygenase-2 (COX-2) in the transition from healthy renal aging to dysfunction, focusing on its involvement in cellular senescence, inflammation, and oxidative stress. Methods: Male Swiss mice aged 3 (young), 12 (middle-aged), and 18 (old) months were analyzed to assess renal function via blood and 24-h urine collection. Protein expression was evaluated by Western blot, and renal collagenase and matrix metalloproteinase 2 (MMP-2) activities were assessed by immunofluorescence. Neutrophil accumulation was measured by myeloperoxidase (MPO) activity, cytokine levels were measured by ELISA, and oxidative stress was assessed by fluorescence. Results: Old mice showed elevated expression of senescence markers (p53, p21, and p16), COX-2, nuclear factor-kappa B (NF-κB p65), and pro-inflammatory cytokines (IL-6, MCP-1), along with increased MPO activity. Collagenase and MMP-2 activities were also enhanced, particularly in glomerular and tubular regions. Furthermore, upregulation of NADPH oxidase subunits and decreased antioxidant enzyme expression resulted in heightened renal ROS production. These molecular changes were accompanied by significant renal dysfunction, as indicated by reduced creatinine clearance and increased albumin-to-creatinine ratio (ACR). Notably, COX-2 expression positively correlated with inflammation, oxidative stress, and renal dysfunction. In contrast, middle-aged mice exhibited early signs of senescence and oxidative stress without overt inflammation or functional impairment. Conclusion: These findings highlight a critical transitional phase in kidney aging, where early senescence and oxidative stress emerge before functional decline. COX-2 may serve as a central mediator in this process, offering a potential therapeutic target for mitigating age-related renal dysfunction.
Upregulation of COX-2 and NADPH Oxidase and Reduced eNOS in Perivascular Adipose Tissue Are Associated With Resistance Artery Dysfunction and Hypertension in Naturally Aged Mice
Grazielle Caroline da Silva, Maisa Nascimento Soares Amaral, Diogo Barros Peruchetti, Virginia Soares Lemos
Journals of Gerontology Series A Biological Sciences and Medical Sciences, 2025
Aging is a major risk factor for cardiovascular disease, with hypertension being the most common outcome. Hypertension often stems from resistance arteries endothelial dysfunction. Recent research highlights the pivotal role of perivascular adipose tissue (PVAT) in regulating endothelial function. We hypothesized that PVAT senescence contributes to vascular dysfunction and hypertension during aging. We showed that naturally aged mice developed hypertension and elevated pro-inflammatory cytokines levels. Moreover, resistance mesenteric arteries showed impaired vascular relaxation that was normalized by apocynin, an antioxidant. The vascular dysfunction was endothelium- and PVAT-dependent, and marked by: decreased nitric oxide- and cyclooxygenase-dependent vascular relaxation, decreased expression of endothelial nitric oxide synthase, and increased cyclooxygenase 2 and NADPH oxidase subunits p22phox and gp91phox expressions in the endothelium and PVAT. Additionally, we observed that PVAT shows greater signs of senescence, particularly with higher p16 expression, indicating that PVAT is more prone to age-related cellular aging. Our findings suggest that in resistance mesenteric arteries PVAT-derived factors are crucial for triggering and amplifying vascular dysfunction in aging, leading to hypertension. The underlying mechanisms involve downregulation of endothelial nitric oxide synthase-derived nitric oxide, NADPH oxidase-dependent oxidative stress, and cyclooxygenase 2-derived vascular contractile factors. This research improves our understanding of the mechanisms behind age-related vascular dysfunction and associated hypertension and opens perspectives for targeted therapeutic strategies.
CD8+ T cells promote tubule-interstitial damage in malaria-induced acute kidney injury
Douglas Esteves Teixeira, Sarah Aparecida dos Santos Alves, Alessandro Sá Pinheiro, Leandro Souza Silva, Rodrigo Pacheco Silva-Aguiar, et al.
Frontiers in Cellular and Infection Microbiology, 2025
IntroductionMalaria acute kidney injury (MAKI) is associated with severe malaria and correlates with poor prognosis and death of patients infected with Plasmodium falciparum. The pathogenesis of MAKI is not completely understood but some hypotheses are well recognized. Host–parasite interactions lead to mechanical obstruction, disorders in the renal microcirculation, and immune-mediated glomerular injury. We investigated the influence of CD8⁺ T cells in the pathogenesis of malaria-induced renal disease.MethodsTo assess the role of T lymphocytes in MAKI pathogenesis, we used adoptive transfer; antibody-driven CD8+ T cells depletion and treatment with FYT720.ResultsThe transference of total T cells isolated from malaria-infected donor mice into naive recipient animals reproduced kidney tubule-interstitial damage without affecting glomerular function. It was associated with increased accumulation of CD8+ T cells in the kidneys of recipient mice. The selective depletion of CD8+ T cells in infected animals resulted in protection from tubular injury, although glomerular alterations still occurred. Finally, we evaluated FTY720, an immunomodulatory drug that sequesters T cells in lymphoid organs and limits their migration, as a potential therapeutic strategy. Treatment with FTY720 prevented the development of proteinuria and the increase in the urine to creatinine ratio. Moreover, FTY720 reduced urinary γ-glutamyl transferase (γ-GT) levels, a marker of tubular injury, but did not alter plasma urea and creatinine, two markers of glomerular function.DiscussionOur results add new knowledge demonstrating that CD8+ T cells have a specific role in tubule-interstitial injury pathology during MAKI.
The angiotensin II/type 1 angiotensin II receptor pathway is implicated in the dysfunction of albumin endocytosis in renal proximal tubule epithelial cells induced by high glucose levels
Liz G. Afonso, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Sarah A.S. Alves, Alvin H. Schmaier, et al.
Biochimica Et Biophysica Acta General Subjects, 2024
Interaction of Angiotensin-(1−7) with kinins in the kidney circulation: Role of B1 receptors
Elizabeth Pereira Mendes, Danielle Ianzer, Diogo Barros Peruchetti, Robson Augusto Souza Santos, Maria Aparecida Ribeiro Vieira
Peptides, 2024
Preconditioning by Moderate-Intensity Exercise Prevents Gentamicin-Induced Acute Kidney Injury
Esdras Guedes Fonseca, Ana Paula Araújo-Ferreira, Markus Berger, Leda Maria Castro Coimbra-Campos, Roberta Silva Filha, et al.
International Journal of Sports Medicine, 2024
Toll like receptor 4 mediates the inhibitory effect of SARS-CoV-2 spike protein on proximal tubule albumin endocytosis
Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Rodrigo A.S. Peres, Sarah A.S. Alves, et al.
Biochimica Et Biophysica Acta Molecular Basis of Disease, 2024
Receptor-mediated endocytosis in kidney cells during physiological and pathological conditions
Mariana C. Rodrigues, Laura B.F. Oliveira, Maria Aparecida R. Vieira, Celso Caruso-Neves, Diogo B. Peruchetti
Current Topics in Membranes, 2024
Kidney Disease and Proteomics: A Recent Overview of a Useful Tool for Improving Early Diagnosis
Nicolly Emanuelle de Souza Barcelos, Maria Laura Limeres, Ana Flavia Peixoto-Dias, Maria Aparecida Ribeiro Vieira, Diogo B. Peruchetti
Advances in Experimental Medicine and Biology, 2024
Multi-omics Investigations in Endocrine Systems and Their Clinical Implications
Rodrigo Antonio Peliciari-Garcia, Carolina Fonseca de Barros, Ayla Secio-Silva, Diogo de Barros Peruchetti, Renata Marino Romano, et al.
Advances in Experimental Medicine and Biology, 2024
Bradykinin produced during Plasmodium falciparum erythrocytic cycle drives monocyte adhesion to human brain microvascular endothelial cells
Sarah A.S. Alves, Douglas E. Teixeira, Diogo B. Peruchetti, Leandro S. Silva, Luiz Felipe P. Brandão, et al.
Brain Research, 2024
O-Linked GlcNAcylation mediates the inhibition of proximal tubule (Na++K+)ATPase activity in the early stage of diabetes mellitus
Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Rodrigo A.S. Peres, Sarah A.S. Alves, Carolina Novaes-Fernandes, et al.
Biochimica Et Biophysica Acta General Subjects, 2023
Gold nanoparticles reduce tubule-interstitial injury and proteinuria in a murine model of subclinical acute kidney injury
Rodrigo A.S. Peres, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Sarah A.S. Alves, et al.
Biochimica Et Biophysica Acta General Subjects, 2023
Inhibition of SGLT2 co-transporter by dapagliflozin ameliorates tubular proteinuria and tubule-interstitial injury at the early stage of diabetic kidney disease
Raysa S. Farias, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Carlos P. Gomes, Ana Acacia S. Pinheiro, et al.
European Journal of Pharmacology, 2023
Rapamycin treatment induces tubular proteinuria: role of megalin-mediated protein reabsorption
Rodrigo A. S. Peres, Diogo B. Peruchetti, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Carlos P. Gomes, et al.
Frontiers in Pharmacology, 2023
SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells
Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Lucas S. Florentino, Rodrigo A.S. Peres, et al.
Biochimica Et Biophysica Acta Molecular Basis of Disease, 2022
Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives
Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Rodrigo A. S. Peres, Diogo B. Peruchetti, Carlos P. Gomes, et al.
International Journal of Molecular Sciences, 2022
O-GlcNAcylation in Renal (Patho)Physiology
Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Ana Acacia S. Pinheiro, Celso Caruso-Neves, Wagner B. Dias
International Journal of Molecular Sciences, 2022
The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria
Edgleyson C. dos Santos, Leandro S. Silva, Alessandro S. Pinheiro, Douglas E. Teixeira, Diogo B. Peruchetti, et al.
Plos One, 2022
Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin
Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Lucas S. Florentino, Christina M. Takiya, María-Paz Marzolo, et al.
International Journal of Molecular Sciences, 2022
Surface megalin expression is a target to the inhibitory effect of bradykinin on the renal albumin endocytosis
Sarah A.S. Alves, Lucas S. Florentino, Douglas E. Teixeira, Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, et al.
Peptides, 2021
Megalin-mediated albumin endocytosis in renal proximal tubules is involved in the antiproteinuric effect of angiotensin II type 1 receptor blocker in a subclinical acute kidney injury animal model
Diogo B. Peruchetti, Paulo F.R. Barahuna-Filho, Rodrigo P. Silva-Aguiar, Thiago P. Abreu, Christina M. Takiya, et al.
Biochimica Et Biophysica Acta General Subjects, 2021
High doses of essential oil of croton zehntneri induces renal tubular damage
Katarine F. Silva, Diogo B. Peruchetti, Gabriela M. Sirtoli, Christina M. Takiya, Ana Acacia S. Pinheiro, et al.
Plants, 2021
Eugenol disrupts Plasmodium falciparum intracellular development during the erythrocytic cycle and protects against cerebral malaria
Kesley A.O. Pontes, Leandro S. Silva, Edgleyson C. Santos, Alessandro S. Pinheiro, Douglas E. Teixeira, et al.
Biochimica Et Biophysica Acta General Subjects, 2021
A high salt diet induces tubular damage associated with a pro-inflammatory and pro-fibrotic response in a hypertension-independent manner
Douglas Esteves Teixeira, Diogo B. Peruchetti, Mariana C. Souza, Maria G. das Graças Henriques, Ana Acacia S. Pinheiro, et al.
Biochimica Et Biophysica Acta Molecular Basis of Disease, 2020
The renin–angiotensin–aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19
Cássia L. Braga, Rodrigo P. Silva‐Aguiar, Denise Battaglini, Diogo B. Peruchetti, Chiara Robba, et al.
Pharmacology Research and Perspectives, 2020
IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload
Diogo B. Peruchetti, João Luiz Silva-Filho, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Christina M. Takiya, et al.
Frontiers in Physiology, 2020
Role of the renin-angiotensin system in the development of severe COVID-19 in hypertensive patients
Rodrigo Pacheco Silva-Aguiar, Diogo Barros Peruchetti, Patricia Rieken Macedo Rocco, Alvin H. Schmaier, Patrícia Machado Rodrigues e Silva, et al.
American Journal of Physiology Lung Cellular and Molecular Physiology, 2020
PKB is a central molecule in the modulation of Na+-ATPase activity by albumin in renal proximal tubule cells
Diogo B. Peruchetti, Andreson C. Freitas, Vitor C. Pereira, Juliana V. Lopes, Christina M. Takiya, et al.
Archives of Biochemistry and Biophysics, 2019
Kinins Released by Erythrocytic Stages of Plasmodium falciparum Enhance Adhesion of Infected Erythrocytes to Endothelial Cells and Increase Blood Brain Barrier Permeability via Activation of Bradykinin Receptors
Leandro S. Silva, Alessandro S. Pinheiro, Douglas E. Teixeira, Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, et al.
Frontiers in Medicine, 2019
Lithium ameliorates tubule-interstitial injury through activation of the mTORC2/protein kinase B pathway
Douglas E. Teixeira, Diogo B. Peruchetti, Leandro S. Silva, Rodrigo P. Silva-Aguiar, Morgana B. Oquendo, et al.
Plos One, 2019
The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury
Leandro S. Silva, Diogo B. Peruchetti, Rodrigo P. Silva-Aguiar, Thiago P. Abreu, Beatriz K. A. Dal-Cheri, et al.
Plos One, 2018
High glucose reduces megalin-mediated albumin endocytosis in renal proximal tubule cells through protein kinase Bo-glc nacylation
Diogo de Barros Peruchetti, Rodrigo Pacheco Silva-Aguiar, Gabriela Marques Siqueira, Wagner Barbosa Dias, Celso Caruso-Neves
Journal of Biological Chemistry, 2018
LPS Induces mTORC1 and mTORC2 Activation During Monocyte Adhesion
Marcelle C. Ribeiro, Diogo B. Peruchetti, Leandro S. Silva, João L. Silva-Filho, Mariana C. Souza, et al.
Frontiers in Molecular Biosciences, 2018
Interaction between bradykinin B2 and Ang-(1–7) Mas receptors regulates erythrocyte invasion by Plasmodium falciparum
Leandro de Souza Silva, Diogo de Barros Peruchetti, Claudio Teixeira Ferreira-Da Silva, André Teixeira Ferreira-DaSilva, Jonas Perales, et al.
Biochimica Et Biophysica Acta General Subjects, 2016
Uroguanylin modulates (Na+ + K+)ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways
Francisco J. Arnaud-Batista, Diogo B. Peruchetti, Thiago P. Abreu, Nilberto R.F. do Nascimento, Gerhard Malnic, et al.
Biochimica Et Biophysica Acta General Subjects, 2016
Group V secretory phospholipase A2 is involved in tubular integrity and sodium handling in the kidney
João Luiz Silva-Filho, Diogo Barros Peruchetti, Felipe Moraes-Santos, Sharon Schilling Landgraf, Leandro Souza Silva, et al.
Plos One, 2016
5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice
Sharon Schilling Landgraf, Leandro Souza Silva, Diogo Barros Peruchetti, Gabriela Modenesi Sirtoli, Felipe Moraes-Santos, et al.
Plos One, 2014
Mis-regulation of mammalian target of rapamycin (mTOR) complexes induced by albuminuria in proximal tubules
Diogo B. Peruchetti, Jie Cheng, Celso Caruso-Neves, William B. Guggino
Journal of Biological Chemistry, 2014
(Na + K +)-ATPase is a target for phosphoinositide 3-kinase/ protein kinase B and protein kinase C pathways triggered by albumin
Diogo B. Peruchetti, Ana Acacia S. Pinheiro, Sharon S. Landgraf, Mira Wengert, Christina M. Takiya, et al.
Journal of Biological Chemistry, 2011

Diogo Barros Peruchetti

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Scopus Publications