MARIA BEATRIZ CAMARGO MONTEIRO CAILLAUD
Projetos de Pesquisa
Unidades Organizacionais
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Urinary Sediment Transcriptomic and Longitudinal Data to Investigate Renal Function Decline in Type 1 Diabetes(2020) MONTEIRO, Maria Beatriz; PELAES, Tatiana S.; SANTOS-BEZERRA, Daniele P.; THIEME, Karina; LERARIO, Antonio M.; OBA-SHINJO, Sueli M.; MACHADO, Ubiratan F.; PASSARELLI, Marisa; MARIE, Suely K. N.; CORREA-GIANNELLA, Maria LuciaIntroduction: Using a discovery/validation approach we investigated associations between a panel of genes selected from a transcriptomic study and the estimated glomerular filtration rate (eGFR) decline across time in a cohort of type 1 diabetes (T1D) patients. Experimental: Urinary sediment transcriptomic was performed to select highly modulated genes in T1D patients with rapid eGFR decline (decliners) vs. patients with stable eGFR (non-decliners). The selected genes were validated in samples from a T1D cohort (n = 54, mean diabetes duration of 21 years, 61% women) followed longitudinally for a median of 12 years in a Diabetes Outpatient Clinic. Results: In the discovery phase, the transcriptomic study revealed 158 genes significantly different between decliners and non-decliners. Ten genes increasingly up or down-regulated according to renal function worsening were selected for validation by qRT-PCR; the genes CYP4F22, and PMP22 were confirmed as differentially expressed comparing decliners vs. non-decliners after adjustment for potential confounders. CYP4F22, LYPD3, PMP22, MAP1LC3C, HS3ST2, GPNMB, CDH6, and PKD2L1 significantly modified the slope of eGFR in T1D patients across time. Conclusions: Eight genes identified as differentially expressed in the urinary sediment of T1D patients presenting different eGFR decline rates significantly increased the accuracy of predicted renal function across time in the studied cohort. These genes may be a promising way of unveiling novel mechanisms associated with diabetic kidney disease progression.
- MicroRNAs 1915-3p, 2861, and 4532 Are Associated with Long-Term Renal Function Decline in Type 1 Diabetes(2019) MONTEIRO, Maria Beatriz; SANTOS-BEZERRA, Daniele P.; PELAES, Tatiana S.; VAIDYA, Vishal S.; CORREA-GIANNELLA, Maria Lucia
- Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease(2021) LIDBERG, Kevin A.; ANNALORA, Andrew J.; JOZIC, Marija; ELSON, Daniel J.; WANG, Lu; BAMMLER, Theo K.; RAMM, Susanne; MONTEIRO, Maria Beatriz; HIMMELFARB, Jonathan; MARCUS, Craig B.; IVERSEN, Patrick L.; KELLY, Edward J.CYP3A5 is the primary CYP3A subfamily enzyme expressed in the human kidney and its aberrant expression may contribute to a broad spectrum of renal disorders. Pharmacogenetic studies have reported inconsistent linkages between CYP3A5 expression and hypertension, however, most investigators have considered CYP3A5*1 as active and CYP3A5*3 as an inactive allele. Observations of gender specific differences in CYP3A5*3/*3 protein expression suggest additional complexity in gene regulation that may underpin an environmentally responsive role for CYP3A5 in renal function. Reconciliation of the molecular mechanism driving conditional restoration of functional CYP3A5*3 expression from alternatively spliced transcripts, and validation of a morpholino-based approach for selectively suppressing renal CYP3A5 expression, is the focus of this work. Morpholinos targeting a cryptic splice acceptor created by the CYP3A5*3 mutation in intron 3 rescued functional CYP3A5 expression in vitro, and salt-sensitive cellular mechanisms regulating splicing and conditional expression of CYP3A5*3 transcripts are reported. The potential for a G-quadruplex (G4) in intron 3 to mediate restored splicing to exon 4 in CYP3A5*3 transcripts was also investigated. Finally, a proximal tubule microphysiological system (PT-MPS) was used to evaluate the safety profile of morpholinos in proximal tubule epithelial cells, highlighting their potential as a therapeutic platform for the treatment of renal disease.