Department of Plastic and Cosmetic Surgery, Shanghai Eighth People's Hospital, Shanghai, China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Diabetes. 2022 Jul 1;71(7):1562-1578. doi: 10.2337/db21-0724.
Cutaneous wound healing in diabetes is impaired and would develop into nonhealing ulcerations. However, the molecular mechanism underlying the wound-healing process remains largely obscure. Here, we found that cutaneous PDGFRα+ fibroblast-expressing lncRNA-H19 (lncH19) accelerates the wound-healing process via promoting dermal fibroblast proliferation and macrophage infiltration in injured skin. PDGFRα+ cell-derived lncH19, which is lower in contents in the wound-healing cutaneous tissue of patients and mice with type 2 diabetes, is required for wound healing through promoting proliferative capacity of dermis fibroblasts as well as macrophage recruitments. Mechanistically, lncH19 relieves the cell cycle arrest of fibroblasts and increases macrophage infiltration in injured tissues via inhibiting p53 activity and GDF15 releasement. Furthermore, exosomes derived from adipocyte progenitor cells efficiently restore the impaired diabetic wound healing via delivering lncH19 to injured tissue. Therefore, our study reveals a new role for lncRNA in regulating cutaneous tissue repair and provides a novel promising insight for developing clinical treatment of diabetes.
糖尿病患者的皮肤创伤愈合受损，会发展成难以愈合的溃疡。然而，创伤愈合过程的分子机制在很大程度上仍不清楚。在这里，我们发现皮肤中表达 PDGFRα+成纤维细胞的长链非编码 RNA-H19（lncH19）通过促进皮肤成纤维细胞增殖和巨噬细胞浸润加速伤口愈合。在 2 型糖尿病患者和糖尿病小鼠的伤口愈合皮肤组织中，含量较低的 PDGFRα+细胞衍生的 lncH19 通过促进真皮成纤维细胞的增殖能力和巨噬细胞募集来促进伤口愈合。在机制上，lncH19 通过抑制 p53 活性和 GDF15 的释放来减轻成纤维细胞的细胞周期停滞并增加损伤组织中的巨噬细胞浸润。此外，脂肪细胞祖细胞衍生的外泌体通过将 lncH19 递送至损伤组织，有效地恢复受损的糖尿病伤口愈合。因此，我们的研究揭示了 lncRNA 在调节皮肤组织修复中的新作用，并为开发糖尿病的临床治疗提供了新的有前途的思路。
