Suppression of TRIM72‐mediated endoplasmic reticulum stress facilitates FOXM1 promotion of diabetic ulcer healing.

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions i...

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Publicado en:Wound Repair & Regeneration Vol. 33; no. 1; pp. 1 - 14
Autores principales: Peng, Lingling, Tian, Yaning, Wu, Xiangkai, Liu, Fengqi, Zhou, Mingzhu, Wu, Zixi, Xia, Yumin, Liu, Xiaoming, Cheng, Chuantao
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell Jan/Feb2025
Acceso en línea:Ver este registro en EBSCOhost
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        atl: Suppression of TRIM72‐mediated endoplasmic reticulum stress facilitates FOXM1 promotion of diabetic ulcer healing.
      aug:
        au:
          Peng, Lingling
          Tian, Yaning
          Wu, Xiangkai
          Liu, Fengqi
          Zhou, Mingzhu
          Wu, Zixi
          Xia, Yumin
          Liu, Xiaoming
          Cheng, Chuantao
        affil: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
      sug:
        subj:
          Transcription Factors Physiology
          DNA-Binding Proteins Physiology
          Carrier Proteins Physiology
          Endoplasmic Reticulum Stress
          Diabetic Foot
          Wound Healing
          Cell Physiology
          Human
          Animal Studies
          Mice
          Immunohistochemistry
          Gene Expression
          Cell Line
          In Vitro Studies
          Cell Proliferation
          Cell Movement
          Biological Assay
          Funding Source
      ab: Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif‐containing protein 72 (TRIM72)‐mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5′‐monophosphate‐activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1‐overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72‐mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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