LUIZ FERNANDO ONUCHIC
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
63 resultados
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- Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain(2019) BARBOSA NETO, Jose Osvaldo; GARCIA, Joao Batista Santos; CARTAGENES, Maria do Socorro de Souza; AMARAL, Andressa Godoy; ONUCHIC, Luiz Fernando; ASHMAWI, Hazem AdelBackgroundExperimental studies suggest that testosterone reduces the nociceptive response after inflammatory and neuropathic stimuli, however the underlying mechanisms have not been fully elucidated. The aims of this study were to evaluate the effect of peripheral blockade of testosterone on pain behaviour and on expression levels of the genes that encode the NaV1.7 and NaV1.8 channels, in dorsal root ganglia in an acute postoperative pain model, as well as the influence of androgen blockade on the expression of these genes.MethodsPostoperative pain was induced by a plantar incision and the study group received flutamide to block testosterone receptor. The animals were submitted to behavioural evaluation preoperatively, 2h after incision, and on the 1st, 2nd, 3rd and 7th postoperative days. Von Frey test was used to evaluate paw withdrawal threshold after mechanical stimuli and the guarding pain test to assess spontaneous pain. The expression of the genes encoding the sodium channels at the dorsal root ganglia was determined by real time quantitative polymerase chain reaction.ResultsAnimals treated with flutamide presented lower paw withdrawal threshold at the 1st, 2nd, 3rd, and 7th postoperative days. The guarding pain test showed significant decrease in the flutamide group at 2h and on the 3rd and 7th postoperative days. No difference was detected between the study and control groups for the gene expression.ConclusionsOur data suggest an antinociceptive effect of androgens following plantar incision. The expression of genes that encode voltage-gated sodium channels was not influenced by androgen blockade.
conferenceObject N-ACETYLCYSTEINE IMPROVES SURVIVAL, RENAL AND CARDIAC PHENOTYPES IN Pkd1-DEFICIENT CYSTIC MICE(2016) MOYSES, Zenaide P.; BASTOS, Ana P.; BALBO, Bruno E.; GARNICA, Margoth R.; CURI-SALEMI, Vera M.; ONUCHIC, Luiz F.conferenceObject Integrated Analyses of Gene, Protein and miRNA Expression in Bladder Cancer Patients Reveals a Link Between mTOR and Differentiation(2018) SCHULTZ, Luciana; CAMILLO, Claudia; SCHULTZ, Andre; PUGA, Renato; CASTRO, Isac de; CHANDRASHEKAR, Darshan S.; SPAGNUL, Samuel J.; CUNHA, Isabela W. da; VARAMBALLY, Sooryanarayana; NETTO, George J.; ONUCHIC, Luiz F.; SOARES, Fernando- Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease(2011) BASTOS, A. P.; ONUCHIC, L. F.Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC2 is a non-selective cation channel permeable to Ca(2+), while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca(2+) signaling. The intracellular Ca(2+) homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin ( mTOR) and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.
bookPart Nefropatias hereditárias não císticas(2022) NEVES, Precil Diego Miranda de Menezes; WATANABE, Elieser Hitoshi; ONUCHIC, Luiz Fernando- Cardiac structural and functional findings in Persian cats with autosomal dominant polycystic kidney disease(2020) GUERRA, Juliana Mariotti; PELLEGRINO, Arine; DANIEL, Alexandre Goncalves Teixeira; FREITAS, Mariana Ferreira de; CARDOSO, Natalia Cavalca; PESSOA, Rebecca Bastos; LUCCA, Gabriel Garone de; LARSSON, Maria Helena Matiko Akao; ONUCHIC, Luiz Fernando; QUEIROGA, Felisbina Luisa; COGLIATI, BrunoAutosomal dominant polycystic kidney disease (ADPKD) has been related to left ventricular structural and functional abnormalities in human patients. The present study aimed to evaluate the cardiac structural and functional findings in Persian cats with ADPKD. Client-owned ADPKD (n=12) and non-ADPKD (n 12) Persian cats were enrolled in this study. The animals underwent echo- and electrocardiographic (ECG) examinations, and non-invasive measurements of systolic blood pressure (SBP) were obtained. Both groups were similar regarding hematological and biochemical parameters, including white blood cell count and levels of blood urea nitrogen, creatinine, total protein and thyroxine. There were no differences related to ECG parameters between ADPKD and non-ADPKD cats. Left ventricular hypertrophy (LVH) was demonstrated in 6/12 (50%) normotensive ADPKD cats with preserved renal function. There were no differences between animal groups regarding the echocardiographic parameters, including left ventricular ejection fraction and shortening fraction; however, basal interventricular septal thickness at end-diastole near the left ventricular outflow tract and aortic artery flow velocity showed slightly elevated values in ADPKD-cats. Our study revealed that Persian cats with ADPKD do not reproduce the functional and structural cardiac phenotype reported in human patients; however, large-scale cohort studies are necessary to distinguish the possibilities of a true linkage between ventricular myocardial hypertrophy and ADPKD in this breed.
- Giant Renal Angiomyolipoma Following Ovarian Stimulation Therapy(2018) WATANABE, Elieser H.; NEVES, Precil D.; BALBO, Bruno E.; SAMPAIO, Carlos A.; ONUCHIC, Luiz F.Renal angiomyolipomas (AMLs) are benign tumors with higher prevalence in women. Female hormones have been shown to induce AML enlargement. This case refers to a 40-year-old woman with 4 left kidney AMLs, the larger ones with 1.0 and 1.3 cm. Ten months after ovarian stimulation for egg harvesting, a computed tomography revealed an 18-cm AML with large-caliber vessels. Given her high risk of AML bleeding, the patient was submitted to selective arterial embolization, which turned out unsuccessful, supporting a plan of nephron-sparing surgery. Our case highlights the pro-growth effects of female hormones on AML, with particular emphasis to ovarian stimulation. (C) 2017 Elsevier Inc.
- APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses(2021) WATANABE, Andreia; GUARAGNA, Mara Sanches; BELANGERO, Vera Maria Santoro; CASIMIRO, Fernanda Maria Serafim; PESQUERO, Joao Bosco; FELTRAN, Luciana de Santis; PALMA, Lilian Monteiro Pereira; VARELA, Patricia; NEVES, Precil Diego Miranda de Menezes; LERARIO, Antonio Marcondes; SOUZA, Marcela Lopes de; MELLO, Maricilda Palandi de; LUTAIF, Anna Cristina Gervasio de Brito; FERRARI, Cassio Rodrigues; SAMPSON, Matthew Gordon; ONUCHIC, Luiz Fernando; NOGUEIRA, Paulo Cesar KochBackground APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. Methods Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m(2)] and slow/non-progressors (eGFR > 30 mL/min/1.73 m(2) through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. Results Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. Conclusions Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.
conferenceObject Dendrogram Analyses of Relative Expression Between Bladder Cancers and Controls Identify PTEN-HIF1 alpha Association as an Alteration Characteristic of Malignancy(2015) SCHULTZ, Luciana; COUTINHO-CAMILLO, Claudia; CASTRO, Isac; DAMM, Gilcy; SPAGNUL, Samuel; CUNHA, Isabela; ONUCHIC, Luiz; SOARES, Fernando- Disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice(2022) AMARAL, Andressa G.; SILVA, Camille C. C. da; SERNA, Julian D. C.; HONORATO-SAMPAIO, Kinulpe; FREITAS, Jessica A.; DUARTE-NETO, Amaro N.; BLOISE, Antonio C.; CASSINA, Laura; YOSHINAGA, Marcos Y.; CHAVES-FILHO, Adriano B.; QIAN, Feng; MIYAMOTO, Sayuri; BOLETTA, Alessandra; BORDIN, Silvana; KOWALTOWSKI, Alicia J.; ONUCHIC, Luiz F.Cardiovascular manifestations account for marked morbi-mortality in autosomal dominant polycystic kidney disease (ADPKD). Pkd1- and Pkd2-deficient mice develop cardiac dysfunction, however the underlying mechanisms remain largely unclear. It is unknown whether impairment of polycystin-1 cleavage at the G-proteincoupled receptor proteolysis site, a significant ADPKD mutational mechanism, is involved in this process. We analyzed the impact of polycystin-1 cleavage on heart metabolism using Pkd1V/V mice, a model unable to cleave this protein and with early cardiac dysfunction. Pkd1V/V hearts showed lower levels of glucose and amino acids and higher lipid levels than wild-types, as well as downregulation of p-AMPK, p-ACC beta, CPT1B-Cpt1b, Ppara, Nppa and Acta1. These findings suggested decreased fatty acid beta-oxidation, which was confirmed by lower oxygen consumption by Pkd1V/V isolated mitochondria using palmitoyl-CoA. Pkd1V/V hearts also presented increased oxygen consumption in response to glucose, suggesting that alternative substrates may be used to generate energy. Pkd1V/V hearts displayed a higher density of decreased-size mitochondria, a finding associated with lower MFN1, Parkin and BNIP3 expression. These derangements were correlated with increased apoptosis and inflammation but not hypertrophy. Notably, Pkd1V/V neonate cardiomyocytes also displayed shifts in oxygen consumption and p-AMPK downregulation, suggesting that, at least partially, the metabolic alterations are not induced by kidney dysfunction. Our findings reveal that disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice, expanding the understanding of heart dysfunction associated with Pkd1 deficiency and likely with human ADPKD.