1. Academic Validation
  2. AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling

AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling

  • Aging (Albany NY). 2020 Apr 14;12(8):6928-6946. doi: 10.18632/aging.103051.
Song Gu 1 2 Hanhao Dai 1 Xilian Zhao 1 Chang Gui 3 Jianchao Gui 1
Affiliations

Affiliations

  • 1 Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, P.R. China.
  • 2 Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
  • 3 Department of Biomedical Engineering, Washington University in St. Louis, MO 63130, USA.
Abstract

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.

Keywords

AKT signaling; AKT3; M2 macrophage; cutaneous wound healing; tissue remodeling.

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