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A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Long noncoding RNA LINC01435 impedes diabetic wound healing by facilitating YY1-mediated HDAC8 expression
Wan Fu1,2, Diefei Liang1,2, Xiaoying Wu1,2
1Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
Abstract:
Abnormal interactions between skin cells play an important role in the dysregulation of diabetic wound recovery. Exosomes are cell-derived lipid nanoparticles that transport messages between cells, and isolating and identifying potential therapeutic noncoding RNAs from exosomes is very important. We demonstrated that treatment with Exos from high glucose-pretreated immortalized human epidermal (HaCaT) cells (HG-Exos) could delay the wound healing process in diabetic mice. Further analysis indicated the Exo-mediated uptake of LINC01435 in recipient human umbilical vein endothelial cells (HUVECs) changes the subcellular localization of the transcription factor Yin Yang 1 (YY1) and cooperates with YY1 to upregulate the expression of histone deacetylases (HDACs)8, resulting in decreased tube formation and ability of HUVECs to migrate, thus angiogenesis was inhibited. These results suggest that LINC01435/YY1/HDAC8 may be an important signaling pathway affecting the recovery of diabetic wounds, which makes it a potential target for the treatment of diabetic foot ulcers.
Insights
High glucose-treated exosomes delay diabetic wound healing by inhibiting blood vessel formation. This involves the LINC01435/YY1/HDAC8 pathway, suggesting a new therapeutic target for diabetic foot ulcers.
Area of Science:
- Cell biology
- Molecular medicine
- Dermatology
Background:
- Diabetic wound healing is often impaired due to abnormal skin cell interactions.
- Exosomes are crucial for intercellular communication, carrying noncoding RNAs that can influence cellular processes.
- Identifying exosomal noncoding RNAs is vital for understanding and treating diabetic wound complications.
Purpose of the Study:
- To investigate the role of exosomes derived from high glucose-pretreated human epidermal cells (HG-Exos) in diabetic wound healing.
- To elucidate the molecular mechanism by which HG-Exos affect endothelial cell function and angiogenesis.
- To identify potential therapeutic targets for diabetic wound recovery.
Main Methods:
- Treatment of diabetic mice with HG-Exos.
- Analysis of exosome-mediated transfer of LINC01435 into human umbilical vein endothelial cells (HUVECs).
- Investigation of the interaction between LINC01435, Yin Yang 1 (YY1), and histone deacetylase 8 (HDAC8) in HUVECs.
- Assessment of HUVEC tube formation and migration assays.
Main Results:
- HG-Exos treatment delayed wound healing in diabetic mice.
- Exosomes facilitated the uptake of LINC01435 by HUVECs.
- LINC01435 altered YY1 subcellular localization and upregulated HDAC8 expression.
- Inhibition of HUVEC tube formation and migration, leading to reduced angiogenesis.
Conclusions:
- The LINC01435/YY1/HDAC8 signaling pathway is implicated in the delayed recovery of diabetic wounds.
- HG-Exos impair angiogenesis by modulating this pathway.
- This pathway represents a potential therapeutic target for diabetic foot ulcers.
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