Project
PULSE project
About us
Who we are
Epidemiological evidence reveals a strong two-way association between Type 2 Diabetes Mellitus (T2DM), Chronic Obstructive Pulmonary Disease (COPD), and asthma. Notably, T2DM prevalence is higher in both COPD (~18–19%) and asthmatic (~28–33%) populations. This overlap points to shared molecular mechanisms, where hyperglycemia, dyslipidemia, and metabolic dysfunction in T2DM may worsen oxidative stress and trigger chronic inflammation in respiratory diseases—highlighting oxidative stress and inflammation as common pathogenic links between metabolic and lung disorders. About this, PNRR: M6/C2_CALL 2022 is a PNRR project which has the objective to research potential new biomarkers associated with these increasingly relevant diseases worldwide.
The research group will be composed of three operative units:
University Hospital - Fondazione Policlinico Tor Vergata, Rome, Italy.
Principal Investigator and project Coordination Prof. Davide Lauro (Director of the UOC Endocrinology and Diabetology).
Responsible for the recruitment and clinical monitoring of patients with T2DM, COPD, and Asthma; conducted in vivo experiments and analyses on small rodents; performed data processing and contributed to the writing of scientific abstracts and papers.
Department of Health Sciences, University Magna Graecia of Catanzaro, Italy.
Unit Coordinator Prof.ssa Marta Greco (Associate Professor of Clinical Pathology).
Responsible for the recruitment and clinical monitoring of patients with T2DM, COPD, and Asthma; identified and analyzed different biomarkers in biological fluids, and performed the data analysis.
University Hospital - Policlinico Paolo Giaccone, Palermo.
Unit Coordinator Prof.ssa Chiara Bellia (Associate Professor of Clinical Biochemistry).
Recruitment of health controls population, mainly recruited from blood donors.
OBJECTIVES
We propose to:
1. Investigate the novel role of peroxiredoxins (Prdxs) and other biomarkers of oxidative stress and inflammation in animal models of diabetes mellitus (DM) and in vitro systems.
2. Explore the role of Prdxs and other biomarkers of oxidative stress and inflammation in diabetic, COPD, and asthmatic populations, comparing them to classical biomarkers.
3. Investigate if Prdxs, oxidative stress, and inflammation biomarkers can be used to monitor treatment response in T2DM, COPD, and asthma.
Three distinct and alternative approaches
Host-Targeting Antivirals (HTAs)
In vivo pre-clinical study will be done, with the relevant endpoints of evaluating glucose metabolism for the diagnosis and for the progression of T2DM. C57BL/6J male mice develop more insulin resistance in response to high fat diet (HFD) regimen and are largely used for the study of T2DM, since HFD causes hyperglycemia, hyperinsulinemia and fatty liver disease, without a severe reduction of functional pancreatic beta-cell mass (Alexander J et al.). Therefore, HFD C57BL/6J and PRDX-6-/- mice (C57BL/6J:129SvJ) will be used to investigate the role of Prdx-6 in the treatment of T2DM.
Mechanistic-Informed Phenotypic Approach
We will investigate whether Prdxs and other oxidative stress and inflammation biomarkers could serve as novel indicators of disease severity in patients with T2DM, COPD, or asthma. In this cross-sectional clinical study, three different cohorts of 300 individuals, 60 with T2DM, 60 with COPD, 60 with asthma, 60 with both of DMT2 and COPD, and 60 with both of DMT2 and asthma will be enrolled. A healthy control population was also enrolled. plasma TLRs ligands (Endotoxin, S100 Protein, HSP60, HSP70, CML, hyaluronan, GAS6 and HMGB1), peroxiredoxins (Prdxs 1 to 6), oxidized LDL, 8-iso-prostaglandin F2, 8-hydroxy deoxyguanine and soluble Toll-like receptors 2 and 4, tissue-specific adipokines and myokines (leptin, resistin, adiponectin, visfatin, irisin, osteoprotegerin, thrombospondin-1, GDF15, FGF21), and inflammatory cytokines and growth factors (IL-1b, IL-6, IL-12, IL15, VEGF, TNFa, IL-1a, IL-2, IL-4, IL-8, IL-10, INFγ, MCP1, EGF, CD40L and CD40r) will be evaluated with commercial ELISA Kits and/or Multiplex immunoassays (Ella™, ProteinSimple, Bio-Techne, San Jose, CA, USA and Evidence Investigator, Randox Labs, Crumlin, UK) analysis using standard protocols.
In vitro experiments
Murine insulinoma cell line (MIN6), EndoC-ßH1 an immortalized human beta cell line and, a human intestinal L cell line (NCI-H716) will be used to study the role of Prdx-6 as a hypoglycemic agent with insulin and GLP-
FUNDING DETAILS
Funder: Project funded under the National Recovery and Resilience Plan (NRRP), Finanziato dall'Unione Europea - Next Generation EU - Missione 6 - Componente 2 - Investimento 2.1 "Valorizzazione e Potenziamento della Ricerca Biomedica del SSN”, Ministero della Salute, Direzione generale della ricerca e dell’innovazione in sanità.
Project title: Role of Peroxiredoxin-6 as New Insulin and GLP-1 secretagogue agent and Peroxiredoxins as Common Soil In Type 2 Diabetes, COPD and Asthma CUP E57G22000340001.
Project Code: PNRR-POC-2022-12376842.
Project total financing: € 1.000.000
Start date: 20/05/23