Bioactive Sphingolipids and Wound Healing
Abstract
Difficult to heal wounds are of significant health concern for military personnel and their family, especially those linked to diabetes, since diabetes has reached epidemic proportions in the Western Society. Despite being linked to high mortality, low quality of life and other health complications, wounds that are difficult to heal are still a mystery, and most pharmacologic regimens are ineffective. One of the key finding of this this proposal is that sphingomyelinase, a protein that exhibit regulatory function and determines the extent of inflammation and proliferation at the wound site is defective during obesity and this insufficiency leads to exacerbation of TNF-alpha production by macrophages. More importantly we show that addition of the product of this protein, termed ceramide or its metabolites to the wounds helps wound repair and decreases pain-associated with these wounds in the mouse. Someone unexpectedly we also found that the mechanisms by which ceramide and its key metabolite, Sphingosine-1-phosphate facilitate wound repair are distinct, evident by a distinct temporal pattern of healing of wounds following the treatment with ceramide and with Sphingosine-1-phosphate. Overall, our experiments confirm the main hypothesis and indicate that ceramide, and sphingosine-1-phosphate are likely therapeutic tools to help the wound healing process in diabetic patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2018
- Accession Number
- AD1063935
Entities
People
- Mariana Nikolova-karakashian
Organizations
- University of Kentucky