Validation of candidate mRNAs and miRNAs as biomarkers of diabetic nephropathy in ...
| Grant number: | 14/15971-4 |
| Support type: | Regular Research Grants |
| Duration: | September 01, 2015 - February 28, 2018 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Maria Elizabeth Rossi da Silva |
| Grantee: | Maria Elizabeth Rossi da Silva |
| Home Institution: | Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Assoc. researchers: | Aritania Sousa Santos ; Edecio Cunha Neto ; Ludmila Rodrigues Pinto Ferreira Camargo |
Abstract
Serum expression of microRNAs in type 1 autoimmune diabetesType 1 autoimmune diabetes mellitus (T1D) is characterized by the specific destruction of pancreatic ² cells and deficiency of insulin production, resulting from immunological attack mediated by lymphocyte, macrophages and NK cells, configuring the insulitis.Faced with the difficulty of obtaining pancreatic tissue samples in humans, much of the knowledge of the pathophysiology of T1D comes from studies in animal models, which do not always express the same mechanisms. In parallel, there are low specific markers in peripheral blood. Further, the main component of genetic predisposition to T1D (HLA-DR and DQ alleles) is shared by 40-50% of the normal population. The presence of anti-islet autoantibodies does not necessarily imply disease progression and does not reflect the beta-cell function, justifying the need to define biomarkers that can show the process of destruction and regeneration of pancreatic beta cells.Recently, a new mechanism of posttranscriptional gene regulation played by single-stranded non-coding small RNAs of 21-25 nucleotides, termed microRNAs have been implicated in the formation and function of pancreatic endocrine cells, insulin secretion and also in regulation the innate and adaptive immunity. Studies have shown that expression in the blood can mirror its aberrant expression in the pancreas. They are also markers of inflammation.Study justificationConsidering the association between microRNA markers of inflammation and beta cell function in peripheral blood and pancreas, we chose to analyze the profile of microRNAs by micro-array in serum samples from pre-diabetic patients and patients with new-onset T1D and compare them with those of normal controls.This evaluation will verify the expression of these markers in a phase preceding the disease, as well as at the stage where the autoimmune process is still active (up to 6 months) and after the destruction of ² cells (2-5 years of diagnosis), periods where there is no interference from structural changes in organs and tissues, resulting from the chronic complications of diabetes.The expression of miRNAs, along with pancreatic autoantibodies and C-peptide levels, can provide important information about the immunological attack, the functionality and the destruction of beta cells. (AU)