Novel Long Noncoding RNA lnc-URIDS Delays Diabetic Wound Healing by Targeting Plod1

被引：39

作者：

Hu, Mengdie ^{[1
]}

Wu, Yuxi ^{[1
]}

Yang, Chuan ^{[1
]}

Wang, Xiaoyi ^{[1
]}

Wang, Wei ^{[1
]}

Zhou, Liyan ^{[1
]}

Zeng, Tingting ^{[1
]}

Zhou, Jing ^{[1
]}

Wang, Chuan ^{[1
]}

Lao, Guojuan ^{[1
]}

Yan, Li ^{[1
]}

Ren, Meng ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Endocrinol, Guangzhou, Peoples R China

来源：

DIABETES | 2020年 / 69卷 / 10期

基金：

中国国家自然科学基金;

关键词：

LOWER-LIMB AMPUTATIONS; EPIGENETIC REGULATION; COLLAGEN; MECHANISMS; EXPRESSION; INCRNAS;

D O I：

10.2337/db20-0147

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Impaired wound healing is one of the main causes of diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes is not fully understood. Long noncoding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. In this study, we identified a novel lncRNA, MRAK052872, named lncRNA UpRegulated in Diabetic Skin (lnc-URIDS), which regulates wound healing in diabetes. lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment in vitro and accelerated diabetic wound healing in vivo. Mechanistically, lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. The findings of the current study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.

引用

页码：2144 / 2156

页数：13

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