4.7 Article

lncRNA-H19 in Fibroblasts Promotes Wound Healing in Diabetes

Journal

DIABETES
Volume 71, Issue 7, Pages 1562-1578

Publisher

AMER DIABETES ASSOC
DOI: 10.2337/db21-0724

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Funding

  1. Xuhui District Medical Research Project of Shanghai [SHXH201802, SHXH201606]
  2. Shanghai Municipal Key Clinical Specialty [shslczdzk00901]

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In this study, it was found that PDGFR alpha(+) fibroblast-expressing lncRNA-H19 plays an important role in promoting wound healing. This lncRNA accelerates wound healing by promoting dermal fibroblast proliferation and macrophage infiltration, and it does so by inhibiting p53 activity and GDF15 releasement.
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 PDGFR alpha(+) fibroblast-expressing lncRNA-H19 (lncH19) accelerates the wound-healing process via promoting dermal fibroblast proliferation and macrophage infiltration in injured skin. PDGFR alpha(+) 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.

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