AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling.
AKT signaling and M2 macrophage-guided tissue repair are key factors in cutaneous wound healing. A delay in this process threatens human health worldwide. However, the role of AKT3 in delayed cutaneous wound healing is largely unknown. In this study, histological staining and transcriptomics demonstrated that prolonged tissue remodeling delayed wound healing. This delay was accompanied by defects in AKT3, collagen alpha-1(I) chain (COL1A1), and collagen alpha-1(XI) chain (COL11A1) expression and AKT signaling. The defect in AKT3 expression was M2 macrophage-specific, and decreased AKT3 protein levels were observed in CD68/CD206-positive macrophages from delayed wound tissue. Downregulation of AKT3 in M2 macrophages did not influence cell polarization but impaired collagen organization by inhibiting COL1A1 and COL11A1 expression in human skin fibroblasts (HSFs). Moreover, a co-culture model revealed that the downregulation of AKT3 in the human monocytic cell line (THP-1)-derived M2 macrophages impaired HSF proliferation and migration. Finally, cutaneous wound healing in AKT3-/- mice was much slower than that of AKT3+/+ mice, and F4/80 macrophages from the AKT3-/- mice had an impaired ability to promote wound healing. Thus, the downregulation of AKT3 in M2 macrophages prolonged tissue remodeling and delayed cutaneous wound healing.
['Gu|Song|S|', 'Dai|Hanhao|H|', 'Zhao|Xilian|X|', 'Gui|Chang|C|', 'Gui|Jianchao|J|']
D000818:Animals D015703:Antigens, CD D015214:Antigens, Differentiation, Myelomonocytic D002460:Cell Line D002465:Cell Movement D049109:Cell Proliferation D018920:Coculture Techniques D024042:Collagen Type I D000090602:Collagen Type I, alpha 1 Chain D024161:Collagen Type XI D015536:Down-Regulation D005109:Extracellular Matrix D005347:Fibroblasts D055785:Gene Knockdown Techniques D006801:Humans D008264:Macrophages D008562:Membrane Glycoproteins D051379:Mice D018345:Mice, Knockout D051057:Proto-Oncogene Proteins c-akt D012333:RNA, Messenger D011971:Receptors, Immunologic D015398:Signal Transduction D012867:Skin D012879:Skin Physiological Phenomena D014945:Wound Healing D014947:Wounds and Injuries
AKT3 M2 macrophage cutaneous wound healing tissue remodeling AKT signaling