1. Stem cell therapy with CRISPR/Cas9-mediated MALAT1 delivery modulates miR-142 and rescues wound healing in rats with age-associated diabetic foot ulcers.
- Author
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Shi, Rongfeng, Chen, Cong, Zhao, Suming, Yuan, Hongxin, Zhao, Jianmei, and Zhao, Hui
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RNA metabolism , *STEM cell transplantation , *TREATMENT of diabetic foot , *RNA physiology , *WOUND healing , *BIOLOGICAL models , *IN vitro studies , *INJECTIONS , *CELLULAR therapy , *AGE distribution , *ANIMAL experimentation , *WESTERN immunoblotting , *MICRORNA , *AMINOGLYCOSIDES , *RNA , *RATS , *CRISPRS , *VASCULAR diseases , *POLYMERASE chain reaction , *CELL lines - Abstract
• MALAT1 is key for diabetic foot ulcer healing in rats. • High glucose reduces MALAT1 in stem cells, affecting ulcers. • MiR-142 regulates genes crucial for diabetic ulcer healing. • Studies show MALAT1′s role in age-related diabetic ulcers. • Stem cell therapy promising for elderly diabetic foot ulcers. Diabetic foot ulcer (DFU) is a serious diabetes complication, significantly impacting the quality of life, particularly in the elderly. Age-associated DFUs pose additional challenges due to impaired healing mechanisms. Our study aims to explore the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a miR-142 sponge in repairing diabetic rat foot ulcer tissue under age-associated diabetes, offering a new theoretical basis and therapeutic target for preventing and treating diabetic vascular disease in the elderly. Using qPCR, we analyzed MALAT1 and miR-142 expression in EPCs and hUC-MSCs. Targetscan predicted potential interaction targets for MALAT1 and miR-142, confirmed by dual luciferase reporter gene assay. An age-associated diabetic rat model was established using Streptozotocin (STZ) injection. Hypoxia, apoptosis, and angiogenesis-related proteins were assessed through Western Blot. In vitro, miR-142 inhibition and MALAT1 overexpression promoted foot ulcer healing in diabetic rats. MALAT1 acted as a miR-142 sponge, downregulated in hUC-MSCs under high glucose, relevant to age-associated diabetic foot ulcers. MiR-142 negatively regulated SIRT1 and Nrf2. In vitro experiments demonstrated potential significance for age-related DFU treatment. MALAT1 in human umbilical cord mesenchymal stem cells expedited foot ulcer healing in diabetic rats, particularly in age-associated diabetes, through miR-142 sponge activity. These findings offer insights for novel therapeutic strategies targeting elderly diabetic foot ulcers, emphasizing exogenous stem cell transplantation's potential in effective DFU treatment for the elderly. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
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