circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models

circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models

09 May 2024 | Qilin Huang, Ziqiang Chu, Zihao Wang, Qiankun Li, Sheng Meng, Yao Lu, Kui Ma, Shengnan Cui, Wenzhi Hu, Wenhua Zhang, Qian Wei, Yanlin Qu, Haihong Li, Xiaobing Fu, Cuiping Zhang
This study investigates the therapeutic potential of circCDK13-loaded small extracellular vesicles (sEVs) in diabetic wound healing. CircCDK13, a circular RNA, was identified as a downregulated molecule in diabetic wounds and shown to stimulate the proliferation and migration of human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) by interacting with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in an N6-methyladenosine (m6A)-dependent manner. Engineered sEVs overexpressing circCDK13 (circCDK13^OE-sEVs) were constructed and shown to accelerate wound healing in both type II diabetic mice (db/db) and type I diabetic rats. The results indicate that circCDK13^OE-sEVs restore the functions of age-related end products (AGEs)-induced HDFs and HEKs in vitro and promote wound healing in diabetic animals. The mechanism involves the formation of a circCDK13-IGF2BP3-CD44/c-MYC ternary complex, which enhances the stability of CD44 and c-MYC mRNAs. This study suggests that circCDK13^OE-sEVs may represent a promising therapeutic strategy for diabetic wound healing.This study investigates the therapeutic potential of circCDK13-loaded small extracellular vesicles (sEVs) in diabetic wound healing. CircCDK13, a circular RNA, was identified as a downregulated molecule in diabetic wounds and shown to stimulate the proliferation and migration of human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) by interacting with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in an N6-methyladenosine (m6A)-dependent manner. Engineered sEVs overexpressing circCDK13 (circCDK13^OE-sEVs) were constructed and shown to accelerate wound healing in both type II diabetic mice (db/db) and type I diabetic rats. The results indicate that circCDK13^OE-sEVs restore the functions of age-related end products (AGEs)-induced HDFs and HEKs in vitro and promote wound healing in diabetic animals. The mechanism involves the formation of a circCDK13-IGF2BP3-CD44/c-MYC ternary complex, which enhances the stability of CD44 and c-MYC mRNAs. This study suggests that circCDK13^OE-sEVs may represent a promising therapeutic strategy for diabetic wound healing.
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Understanding circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models