<< Back to the abstract archive
Low Abundance Of Microrna-21 In Diabetic Wound Macrophages Compromises Resolution Of Inflammation
Amitava Das, Mithun Sinha, Pradipta Banerjee, Nirupam Biswas, Savita Khanna, Chandan K. Sen and Sashwati Roy
Indiana Center for Regenerative Medicine and Engineering (ICRME)
2019-02-18
Presenter: Amitava Das
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: Chandan K. Sen
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Unresolved inflammation impairs diabetic wound healing. Previous work by our laboratory have demonstrated decreased clearance of apoptotic cells (efferocytosis) by diabetic wound macrophages (wmϕ) compromises timely resolution of wound inflammation. Interestingly, delivery of miR-21 to human monocyte-derived macrophages (MDM) bolsters efferocytosis resulting in a net anti-inflammatory phenotype. Thus we hypothesized that diabetic wound macrophages have lower abundance of miR-21 that leads to persistent inflammation. To address our hypothesis, wmϕ was isolated from well-developed negative-pressure wound therapy (NPWT) dressings (for human) and subcutaneously implanted PVA sponges (for mice). Both human and murine diabetic wmϕ showed significantly lower miR-21 levels compared to non-diabetics (p< 0.05; n=4). To determine the significance of lower miR-21 in wmϕ fate and resolution of inflammation, a myeloid cell-specific miR-21 knockdown mice (miR-21mϕ£G/£G) was developed in our laboratory by crossbreeding mice carrying floxed miR-21 allele (miR-21fl/fl) with LysM-Cre mice. Wounds of miR-21mϕ£G/£G animals suffered from increased neutrophil abundance and persistent inflammation characterized by increased TNF-ƒÑ and lower IL-10 (p<0.05; n=4). Bioinformatics analysis predicted the neutrophil chemoattractant GRO-£ to be a direct target of miR-21. Using 3¡¦-UTR firefly luciferase reporter, GRO-£ was discovered to be a direct target of miR-21 (p<0.05; n = 4). Lower miR-21 in diabetic and miR-21mϕ£G/£G wmϕ desilenced GRO-£ (p<0.05; n=4) resulting in increased abundance of neutrophils at the wound-edge tissue. This study provides a novel mechanism of miR-21-GRO-£ mediated unresolved inflammation in diabetic wounds.
