Luiz F. Onuchic

Universidade de São Paulo

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Gregory G. Germino

National Institutes of Health

Elieser Hitoshi Watanabe

Universidade de São Paulo

Precil Diego Miranda de Menezes Neves

Universidade de São Paulo

Lisa M. Guay‐Woodford

Children's Hospital of Philadelphia

Stefan Somlo

Yale University

Klaus Zerres

RWTH Aachen University

Andréia Watanabe

Universidade de São Paulo

Bruno Eduardo Pedroso Balbo

Universidade de São Paulo

Ellis D. Avner

Children's Hospital of Wisconsin

Andressa G. Amaral

Universidade de São Paulo

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Universidade de São Paulo

210

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

127

Universidade Brasil

Johns Hopkins University

Universidade Federal de São Paulo

Hospital Universitário da Universidade de São Paulo

Johns Hopkins Medicine

Hospital São Paulo

Pediatric Nephrology of Alabama

Yale University

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Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidney tissues of Pkd1 deficient mouse models

Research Square (Research Square) (2021)

Juan José Augusto Moyano Muñoz Ana Carolina Anauate Andressa G. Amaral Frederico Moraes Ferreira Elieser Hitoshi Watanabe

Abstract Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited renal disorder, characterized by renal cyst development leading to end-stage renal disease. Although the appropriate choice of suitable reference is critical for quantitative RNA analysis, no comparison of frequently used “housekeeping” genes is available. Here, we determined the validity of 7 candidate housekeeping genes ( Actb , Actg1 , B2m , Gapdh , Hprt , Pgam1 and Ppia ) in kidney tissues from mouse models orthologous to ADPKD, including a cystic mice (CY) 10–12 weeks old ( Pkd1 flox/flox : Nestin cre / Pkd1 flox/- : Nestin cre , n = 10) and non-cystic (NC) controls ( Pkd1 flox / flox / Pkd1 flox / - , n = 10), Pkd1 -haploinsufficient (HT) mice ( Pkd1 +/- , n = 6) and wild-type (WT) controls ( Pkd1 +/+ , n = 6) and a severely cystic (SC) mice 15 days old ( Pkd1 V/V , n = 7) and their controls (CO, n = 5). Gene expression data were analyzed using six distinct statistical softwares. The estimation of the ideal number of genes suggested the use of Ppia alone as sufficient, although not ideal, to analyze groups altogether. Actb , Hprt and Ppia expression profiles were correlated in all samples. Ppia was identified as the most stable housekeeping gene, while Gapdh was the least stable for all kidney samples. Stat3 expression level was consistent with upregulation in SC compared to CO when normalized by Ppia expression. In conclusion, present findings identified Ppia as the best housekeeping gene for CY + NC and SC + CO groups, while Hprt was the best for the HT + WT group.

PKD1

Housekeeping gene

10.21203/rs.3.rs-551245/v1

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Supplementary Material for: International Multi-Specialty Delphi Survey: Identification of Diagnostic Criteria for Hepatic and Renal Cyst Infection

Lantinga de Sévaux R.G.L.Ahsan Alam Chantal P. Bleeker‐Rovers Mickaël Bobot

Identification

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Delphi Method

Delphi

10.6084/m9.figshare.3808161.v2

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Bases moleculares e celulares das nefropatias hereditárias císticas

Revista de Medicina (2015)

Andressa G. Amaral Luiz F. Onuchic

<p>As nefropatias hereditárias císticas (NHCs) são causadas por mutações gênicas determinantes ao desenvolvimento de anormalidades nas células renais epiteliais, alterações que criam as condições biológicas necessárias à formação cística. A identificação de genes mutados nessas enfermidades e a caracterização de seus produtos proteicos vêm permitindo a elucidação de mecanismos envolvidos em sua patogênese. Esta revisão tem como foco as bases genéticas e a patogênese molecular dessas enfermidades, embora também aborde brevemente aspectos clínicos e epidemiológicos das NHCs de maior impacto médico e socioeconômico. Dentro deste conjunto de moléstias, abordaremos a doença renal policística autossômica dominante, doença renal policística autossômica recessiva, nefronoftises, doença renal túbulo-intersticial autossômica dominante, doença de von Hippel-Lindau e complexo esclerose tuberosa. Essas NHCs possuem sobreposição de manifestações clínicas e compartilham vias e defeitos moleculares. Entre suas características comuns, destacaremos o papel central de anormalidades no cílio apical primário e de vias de sinalização intracelular responsáveis por alterações fundamentais do fenótipo celular. Ao apresentar os avanços obtidos na patogênese molecular e celular das NHCs, discutiremos criticamente o estabelecimento, os papeis e as implicações da homeostase defeituosa de cálcio citosólico; resposta celular hiperproliferativa ao AMP cíclico; taxas elevadas de proliferação celular e apoptose; alterações da matriz extracelular; alterações da polaridade celular; e secreção transepitelial de fluido. O conhecimento acumulado nas últimas duas décadas trouxe um novo contexto molecular e celular às NHCs, capaz de criar a plataforma de conhecimento necessária para o desenvolvimento de ensaios pré-clínicos. Tais ensaios, por sua vez, vêm amparando a condução de estudos clínicos robustos, os quais têm aberto perspectivas terapêuticas promissoras.</p>

10.11606/issn.1679-9836.v94i4p263-281

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A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family

BMC Nephrology (2019)

Maria Luíza Gonçalves dos Reis Monteiro Fabiano Bichuette Custódio Precil Diego Miranda de Menezes Neves Frederico Moraes Ferreira Elieser Hitoshi Watanabe

Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin.This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality.The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.

Nephrology

Glomerulopathy

10.1186/s12882-019-1507-7

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The Reducing Effect of Sirolimus on Angiomyolipoma is Determined by Decrease of Its Fat-Poor Compartments and Is Associated with Striking Reduction of Vascular Structures

Research Square (Research Square) (2020)

Elieser Hitoshi Watanabe Fernando Morbeck Almeida Coelho Hilton Leão Filho Bruno Eduardo Pedroso Balbo Precil Diego Miranda de Menezes Neves

Abstract Background: Renal angiomyolipomas hemorrhage is strongly associated with their size and vascular constitution. Since previous studies showed that mTOR inhibitors can differentially act in distinct cell lines, we analyzed the effects of sirolimus on the volume of different components of angiomyolipomas in patients with tuberous sclerosis complex, including vascular structures. We retrospectively analyzed 23 angiomyolipomas from 10 patients treated with sirolimus. An approach based on a Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Results: Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments, with a lesser contribution of the intermediate-fat component, while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. Massive reduction of aneurysmatic/ectatic vascular structures was observed, with disappearance of such lesions in most cases. Conclusions: Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels and other vascular structures. Our findings revealed, therefore, the likely mechanism responsible for the reported risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. Our findings also expand the understanding the biology of this tumor, supporting a role for mTOR in maintenance, and maybe assembling, of blood vessels in angiomyolipomas.

Angiomyolipoma

Sirolimus

Ectasia

10.21203/rs.3.rs-17408/v1

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Prenatal Diagnosis of Autosomal Recessive Polycystic Kidney Disease (ARPKD)

The Journal of Urology (1999)

Klaus Zerres Gabi Mücher Jutta Becker C. Steinkamm S. Rudnik-Schnewborn

Polycystic disease

10.1097/00005392-199901000-00136

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Citations (1)

Long-Term Follow-up of a Clinical, Laboratory and Molecular Assessment of a Woman with Jansen Chondrodysplasia Due to aDe NovoMutation in PTHR1

Daniel Fonseca de Carvalho Luiz F. Onuchic Silvia Bertoncello Berenice B. Mendonça Pedro HS Correa

10.1210/endo-meetings.2011.part3.p22.p3-94

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Urological and Kidney Involvements in Amyloidosis

Springer eBooks (2023)

Valkercyo A. Feitosa Luiz F. Onuchic Irene de Lourdes Noronha

10.1007/978-3-031-17759-0_7

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Aumento regulatorio do volume celular em tubulos de malpighi

Resumos (1993)

C Caruso Neves I R Arenstein Luiz F. Onuchic Aníbal Gil Lopes

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Abdominal pain, arthritis, and nephrotic syndrome in a Syrian patient

Clinics (2012)

Bruno Eduardo Pedroso Balbo André Albuquerque Silva Andressa G. Amaral Denise Maria Avancini Costa Malheiros Luiz F. Onuchic

Familial Mediterranean fever (FMF) is an autosomal recessive disorder that is characterized by sporadic paroxysmal attacks of fever and serosal inflammation. Although it occurs primarily in ethnic groups originating in the Mediterranean region, FMF is not restricted to these groups and is still underdiagnosed in nephrology settings in non-Mediterranean countries (1). The disease morbidity is largely associated with recurrent attacks of pain and fever, and mortality is mainly associated with amyloidosis and kidney disease (1). The discovery of colchicine in 1972 led to an effective treatment for FMF in the prevention of acute attacks and secondary amyloidosis, significantly increasing the importance of an accurate and early diagnosis (2). The clinical criteria proposed by Livneh et al. (3) in 1997 continue to be the gold standard for diagnosis. However, limitations arise in atypical cases and in patients of non-Mediterranean origin. The gene mutated in FMF, MEFV (Mediterranean fever), was cloned in 1997, shedding light on the disease pathogenesis and improving the tools for diagnosis (4). In this scenario, genotype-phenotype correlation studies revealed specific alleles that were associated with amyloidosis and kidney disease, and mutation-based analysis, particularly directed toward hot spots, emerged as an essential approach for diagnosis in atypical cases (5).

10.6061/clinics/2012(06)24

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