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Mir-21 Promotes Resolution Of Wound Inflammation Via Facilitating Macrophage Polarization
Pradipta Banerjee, Amitava Das, Chandan K Sen and Sashwati Roy
Indiana University School of Medicine
2019-02-15
Presenter: Pradipta Banerjee
Affidavit:
Sashwati Roy
Director Name: Sashwati Roy
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Wound inflammation aims to restore normal physiological function of injured tissue. Persistent inflammatory response is detrimental and cause loss of organ function. Wound macrophages (wmϕ) play pivotal in resolution of wound inflammation. MicroRNAs (miRs) are small non-coding RNAs that enact post-transcriptional gene silencing. miRs determine the pattern of the injury-inducible transcriptome and therefore healing outcomes. Our lab has previously reported an increased expression of inducible miR-21 in peripheral blood monocyte-derived macrophages following engulment of apoptotic cells (efferocytosis) resulting in a net anti-inflammatory phenotype. To elucidate the significance of wound macrophage miR-21 in wound inflammation, a myeloid specific knock down of miR-21 (miR-21mϕÄ/Ä) was developed by crossbreeding mice carrying floxed miR-21 allele (miR-21fl/fl) with LysM promoter driven crerecombinase mice. Wound macrophages were isolated from subcutaneously implanted PVA sponges which were subjected to repeated compression followed by CD11b positive selection. miR-21 expression was significantly knocked down (>80%) in wmϕ of miR-21mϕÄ/Ä mice. Expression of pro-inflammatory markers in miR-21mϕÄ/Ä wmϕ were significantly higher while those of reparative phenotype was attenuated(p<0.05; n=4) suggesting a shift in the macrophage polarization toward pro-inflammatory phenotype that resulted in persistent inflammation and compromised wound closure (p<0.05; n=4). Macrophage polarization is governed by several transcription factors. Bioinformatics analysis predicted STAT2, a transcription factor that drives macrophage polarization towards pro-inflammatory phenotype, to be a direct target of miR-21. Interestingly STAT2 was wound to be significantly higher in the wmϕ of miR-21mϕÄ/Ä mice. This study provides a novel mechanism of miR-21-STAT2 mediated pathway of wmϕ polarization that controls dermal wound inflammtion.
