Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Inc Country of Publication: United States NLM ID: 8008690 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5169 (Electronic) Linking ISSN: 01969781 NLM ISO Abbreviation: Peptides Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Elsevier Science Inc.
      Original Publication: Fayetteville, N. Y., Ankho International.
    • Subject Terms:
      Autophagy* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/metabolism ; Cathelicidins*/pharmacology ; Diabetes Mellitus, Experimental*/drug therapy; Animals ; Humans ; Mice ; Wound Healing
    • Abstract:
      Diabetic patients often experience impaired wound healing. Human cathelicidin LL-37 possesses various biological functions, such as anti-microbial, anti-inflammatory, and pro-wound healing activities. Autophagy has important effects on skin wound healing. However, little is known about whether LL-37 accelerates diabetic wound healing by regulating autophagy. In the study, we aimed to investigate the role of autophagy in LL-37-induced wound healing and uncover the underlying mechanisms involved. A full-thickness wound closure model was established in diabetic mice to evaluate the effects of LL-37 and an autophagy inhibitor (3-MA) on wound healing. The roles of LL-37 and 3-MA in regulating keratinocyte migration were assessed using transwell migration and wound healing assays. The activation of transcription factor EB (TFEB) was measured using western blotting and immunofluorescence (IF) assays of its nuclear translocation. The results showed that LL-37 treatment improved wound healing in diabetic mice, whereas these effects were reversed by 3-MA. In vitro, 3-MA decreased the effects of LL-37 on promoting HaCat keratinocyte migration in the presence of high glucose (HG). Mechanistically, LL-37 promoted TFEB activation and resulted in subsequent activation of autophagy, as evidenced by increased nuclear translocation of TFEB and increased expression of ATG5, ATG7, and beclin 1 (BECN1), whereas these changes were blocked by TFEB knockdown. As expected, TFEB knockdown damaged the effects of LL-37 on promoting keratinocyte migration. Collectively, these results suggest that LL-37 accelerates wound healing in diabetic mice by activating TFEB-dependent autophagy, providing new insights into the mechanism by which LL-37 promotes diabetic wound healing.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Autophagy; Cathelicidin; Diabetes wound healing; LL-37; TFEB
    • Accession Number:
      0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
      0 (Cathelicidins)
      0 (Tcfeb protein, mouse)
      0 (TFEB protein, human)
    • Publication Date:
      Date Created: 20240229 Date Completed: 20240408 Latest Revision: 20240411
    • Publication Date:
      20240411
    • Accession Number:
      10.1016/j.peptides.2024.171183
    • Accession Number:
      38423213