Gene expression profiles and possible interactions between microRNAs and mRNAs in type 1 Diabetes Mellitus, focusing on response to oxidative stress and DNA repair

• Grant number: 10/12069-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2011
• End date: August 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Elza Tiemi Sakamoto Hojo
• Grantee: Paula Takahashi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 08/56594-8 - Control of the transcriptome in diabetes mellitus, AP.TEM

Abstract

Diabetes mellitus affects over 165 million people worldwide and it is a group of diseases characterized by extracellular chronic hyperglycemia. The latter is a consequence of the deficiency of insulin action and this hormone in turn, is responsible for regulating physiological glucose blood levels. The present study focuses on type 1 diabetes mellitus (T1D), one of the categories of diabetes. This type of diabetes results from an autoimmune process in which the insulin-producing ² cells are eliminated, leading to insulin deficiency; and for this reason, patients affected by T1D are insulin-dependent. They also comprise approximately 10% of the diabetic patients and the great majority of them are children. One of the consequences of hyperglycemia is the increase in the levels of reactive oxygen species (ROS), which can cause DNA damage. Base excision repair (BER) is the major mechanism involved in the repair of oxidative DNA damage, although nucleotide excision repair (NER) and mismatch repair (MMR) have also been implicated. A number of studies have associated the regulation of genes involved in the DNA repair with microRNAs (RNAs composed of 20-25 nucleotides that do not encode any protein but play a role in the negative regulation of many cellular processes). Hence, the present study focuses on investigating the association between T1D and the regulation of genes involved in the oxidative DNA damage repair by microRNAs. In order to accomplish that, we will study the expression profile of microRNAs (by microarrays) and both the gene and protein expression of potential targets of these microRNAs that are implicated in the DNA repair (that will be obtained from the microarray method and whose expression will be confirmed by qPCR) in T1D patients compared to normal subjects (control group).

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

COLLARES, C. V. A.; EVANGELISTA, A. F.; XAVIER, D. J.; TAKAHASHI, P.; ALMEIDA, R.; MACEDO, C.; MANOEL-CAETANO, F.; FOSS, M. C.; FOSS-FREITAS, M. C.; RASSI, D. M.; et al. Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus. MOLECULAR BIOLOGY REPORTS, v. 40, n. 9, p. 5351-5358, SEP 2013. (10/12069-7, 08/56594-8)

MANOEL-CAETANO, FERNANDA S.; XAVIER, DANILO J.; EVANGELISTA, ADRIANE F.; TAKAHASHI, PAULA; COLLARES, CRISTHIANNA V.; PUTHIER, DENIS; FOSS-FREITAS, MARIA C.; FOSS, MILTON C.; DONADI, EDUARDO A.; PASSOS, GERALDO A.; et al. Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease. Gene, v. 511, n. 2, p. 151-160, DEC 15 2012. (10/12069-7, 08/56594-8)

EVANGELISTA, ADRIANE F.; COLLARES, CRISTHIANNA V. A.; XAVIER, DANILO J.; MACEDO, CLAUDIA; MANOEL-CAETANO, FERNANDA S.; RASSI, DIANE M.; FOSS-FREITAS, MARIA C.; FOSS, MILTON C.; SAKAMOTO-HOJO, ELZA T.; NGUYEN, CATHERINE; et al. Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation. BMC MEDICAL GENOMICS, v. 7, MAY 23 2014. (10/12069-7, 08/56594-8)

XAVIER, DANILO J.; TAKAHASHI, PAULA; MANOEL-CAETANO, FERNANDA S.; FOSS-FREITAS, MARIA C.; FOSS, MILTON C.; DONADI, EDUARDO A.; PASSOS, GERALDO A.; SAKAMOTO-HOJO, ELZA T.. One-week intervention period led to improvements in glycemic control and reduction in DNA damage levels in patients with type 2 diabetes mellitus. Diabetes Research and Clinical Practice, v. 105, n. 3, p. 356-363, SEP 2014. (10/12069-7, 08/56594-8)

TAKAHASHI, PAULA; XAVIER, DANILO J.; LIMA, JESSICA E. B. F.; EVANGELISTA, ADRIANE F.; COLLARES, CRISTHIANNA V. A.; FOSS-FREITAS, MARIA C.; RASSI, DIANE M.; DONADI, EDUARDO A.; PASSOS, GERALDO A.; SAKAMOTO-HOJO, ELZA T.. Transcript Expression Profiles and MicroRNA Regulation Indicate an Upregulation of Processes Linked to Oxidative Stress, DNA Repair, Cell Death, and Inflammation in Type 1 Diabetes Mellitus Patients. JOURNAL OF DIABETES RESEARCH, v. 2022, p. 15-pg., 2022-02-01. (08/56594-8, 13/09352-7, 10/12069-7)

XAVIER, DANILO J.; TAKAHASHI, PAULA; EVANGELISTA, ADRIANE F.; FOSS-FREITAS, MARIA C.; FOSS, MILTON C.; DONADI, EDUARDO A.; PASSOS, GERALDO A.; SAKAMOTO-HOJO, ELZA T.. Assessment of DNA damage and mRNA/miRNA transcriptional expression profiles in hyperglycemic versus non-hyperglycemic patients with type 2 diabetes mellitus. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, v. 776, p. 13-pg., 2015-06-01. (08/56594-8, 10/12069-7)

XAVIER, DANILO J.; TAKAHASHI, PAULA; EVANGELISTA, ADRIANE F.; FOSS-FREITAS, MARIA C.; FOSS, MILTON C.; DONADI, EDUARDO A.; PASSOS, GERALDO A.; SAKAMOTO-HOJO, ELZA T.. Assessment of DNA damage and mRNA/miRNA transcriptional expression profiles in hyperglycemic versus non-hyperglycemic patients with type 2 diabetes mellitus. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, v. 776, n. SI, p. 98-110, JUN 2015. (10/12069-7, 08/56594-8)

TAKAHASHI, PAULA; XAVIER, DANILO J.; EVANGELISTA, ADRIANE F.; MANOEL-CAETANO, FERNANDA S.; MACEDO, CLAUDIA; COLLARES, CRISTHIANNA V. A.; FOSS-FREITAS, MARIA C.; FOSS, MILTON C.; RASSI, DIANE M.; DONADI, EDUARDO A.; et al. MicroRNA expression profiling and functional annotation analysis of their targets in patients with type 1 diabetes mellitus. Gene, v. 539, n. 2, p. 213-223, APR 15 2014. (10/12069-7, 08/56594-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

TAKAHASHI, Paula. Gene Expression Profiles and Possible Interactions between microRNAs and mRNAs in Type 1 Diabetes Mellitus, Focusing on Response to Oxidative Stress and DNA Repair. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.