Diabetes Mellitus, hyperglycemic memory and cellular senescence: implications to skin wound healing
Description: Diabetes mellitus (DM) is a disease with a high and growing prevalence worldwide; the occurrence of chronic wounds that are difficult to heal is a common complication of DM. Those wounds have a multifactorial etiology associated with hyperglycemia and can increase mortality associated with the disease. Studies suggest that chronic wounds may be associated with a hyperglycemic memory - even after blood glucose levels are regularized, people with DM remain more prone to its development. However, more studies are needed involving the existence of this memory, as well as the mechanisms involved, probably epigenetic. Likewise, the literature has shown an accumulation of senescent cells in the organs of diabetic individuals, which favors a systemic inflammatory condition. However, the role of senescent cells in healing in diabetics is not yet clear, as there are studies that also point to a beneficial role for these cells. In this project, we seek a better understanding of the mechanisms involved in healing in diabetic mice, examining the role of hyperglycemia (transient and long-lasting) on the induction of senescence in skin tissues, the existence of a hyperglycemic memory and the role of senescent cells in healing process. The participation of senescent cells in healing will also be evaluated through the systemic administration of a combination of senolytic agents (Dasatinib + Quercetin). We also intend to evaluate, in human fibroblasts exposed to a high concentration of glucose, the role of glucose and oxidative stress on the induction of senescence, as well as the participation of specific microRNAs (31, 221 and 222) in senescence and hyperglycemic memory. The identification of potential regulatory agents, such as antioxidants, regulators of miRNA expression (miR mimics or antagomiRs) and senolytics, is of great interest to human health. This is an important and pioneering study and the results obtained could eventually serve as a basis for treatments aimed at limiting the effect of hyperglycemic memory and senescent cells in chronic wounds of diabetic patients. (AU)
Funding type: grant
Funder scheme: Auxílio à Pesquisa - Regular
Start date: 2025-11-01
End date: 2028-10-31
Investigator: Marinilce Fagundes dos Santos
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB)
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 25/14347-0
OpenAlex ID: G415048520