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Diabetes induces myeloid bias in bone marrow progenitors associated with enhanced wound macrophage accumulation and impaired healing.
- Source :
-
The Journal of pathology [J Pathol] 2019 Dec; Vol. 249 (4), pp. 435-446. Date of Electronic Publication: 2019 Aug 28. - Publication Year :
- 2019
-
Abstract
- Diabetes induces dysregulation throughout the spectrum of myeloid lineage cells from progenitors to terminally differentiated cells. Another complication of diabetes is persistent inflammation, including prolonged accumulation of macrophages, which contributes to impaired wound healing. However, it remains unclear whether diabetes disrupts the response of bone marrow progenitors to peripheral injury and whether such dysregulation leads to sustained inflammation and impaired healing. Here, we demonstrated that diabetic mice (db/db, referred to here as DB) exhibit myeloid lineage bias during homeostasis and following injury. In addition, cells in the LSK (Lin <superscript>-</superscript> Sca-1 <superscript>+</superscript> cKit <superscript>+</superscript> ) population of DB mice are preprogrammed towards myeloid commitment at the transcriptional level, and cultured myeloid progenitors from DB mice produce more monocytes ex vivo than their non-diabetic counterparts. We also show via bone marrow transfer between interleukin-1 receptor 1 KO (Il1r1 <superscript>-/-</superscript> ) and DB mice that IL-1R1 signaling is likely not involved in myeloid skewing in DB mice. Furthermore, in vitro experiments indicated that macrophage colony-stimulating factor receptor signaling is not likely involved in enhanced myeloid transcription factor expression in LSK cells of DB mice. Our findings indicate that myeloid lineage commitment in bone marrow may contribute to increased macrophage numbers observed in diabetic skin wounds, and that strategies to regulate monopoiesis during homeostasis or post-wounding may improve diabetic wound healing. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<br /> (© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Subjects :
- Animals
Bone Marrow Transplantation
Cells, Cultured
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 metabolism
Disease Models, Animal
Macrophages metabolism
Mice, Inbred C57BL
Mice, Knockout
Myeloid Progenitor Cells metabolism
Myelopoiesis
Receptor, Macrophage Colony-Stimulating Factor metabolism
Receptors, Interleukin-1 Type I genetics
Receptors, Interleukin-1 Type I metabolism
Signal Transduction
Skin injuries
Skin metabolism
Stem Cell Transplantation
Wounds, Penetrating genetics
Wounds, Penetrating metabolism
Cell Lineage
Diabetes Mellitus, Type 2 pathology
Macrophages pathology
Myeloid Progenitor Cells pathology
Skin pathology
Wound Healing
Wounds, Penetrating pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9896
- Volume :
- 249
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 31342513
- Full Text :
- https://doi.org/10.1002/path.5330