c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells

Abstract

Objective. Mesenchymal stem cells (MSCs) are considered a promising therapy for wound healing. Here, we explored the role of c-Jun in diabetic wound healing using human umbilical cord-derived MSCs (hUC-MSCs). Methods. Freshly isolated hUC-MSCs were subjected to extensive in vitro subcultivation. The cell proliferative and migratory capacities were assessed by the Cell Counting Kit-8 and scratch assays, respectively. c-Jun expression was evaluated by RT-PCR and western blot analysis. The function of c-Jun was investigated with lentivirus transduction-based gene silencing and overexpression. Diabetes mellitus was induced in SD rats on a high-glucose/fat diet by streptozocin administration. Wounds were created on the dorsal skin. The effects of c-Jun silencing and overexpression on wound closure by hUC-MSCs were examined. Reepithelialization and angiogenesis were assessed by histological and immunohistochemical analysis, respectively. Platelet-derived growth factor A (PDGFA), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) levels were determined by western blot analysis. Results. hUC-MSCs showed gradually decreased cell proliferation, migration, and c-Jun expression during subcultivation. c-Jun silencing inhibited cell proliferation and migration, while c-Jun overexpression enhanced proliferation but not migration. Compared with untransduced hUC-MSCs, local subcutaneous injection of c-Jun-overexpressing hUC-MSCs accelerated wound closure, enhanced angiogenesis and reepithelialization at the wound bed, and increased PDGFA and HGF levels in wound tissues. Conclusion. c-Jun overexpression promoted hUC-MSC proliferation and migration in vitro and accelerated diabetic wound closure, reepithelization, and angiogenesis by hUC-MSCs in vivo. These beneficial effects of c-Jun overexpression in diabetic wound healing by hUC-MSCs were at least partially mediated by increased PDGFA and HGF levels in wound tissues.

Angelica Dahurica Regulated the Polarization of Macrophages and Accelerated Wound Healing in Diabetes: A Network Pharmacology Study and In Vivo Experimental Validation

“…Thereby, it has a critical role in the cutaneous healing of wounds (Li et al, 2003). Another research reported by Yue et al found that the overexpression of c-JUN improves the rapidity at which wounds heal in diabetic rats (Yue et al, 2020). Accordingly, the results suggest that A. dahurica may improve the rate at which wounds heal through several targets, is consistent with the idea of TCM.…”

Study on the Mechanism of Periplaneta americana Extract to Accelerate Wound Healing after Diabetic Anal Fistula Operation Based on Network Pharmacology

“…Compared with the control group, skin damage caused the upregulation of TNF-α expression in the peripheral blood of diabetic rats and a significant increase in M1 macrophage infiltration, which proved that the high-glucose environment that was caused by single nuclear cells is more prone to the polarization of M1 type macrophages. Yue [23] proposed that c-Jun overexpression promotes the proliferation and migration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in vitro and accelerates diabetic wound healing, re-epithelialization, and angiogenesis through hUC- [24,25]. In the pathogenesis of diabetic wounds, the expression level of MMP9 increases, impairing the balance of ECM synthesis, and degradation can cause the wound to be difficult to heal.…”

Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis

“…At present, there are some data indicating that MSCs might improve complications from DM [9][10][11]. We conducted this systematic review and meta-analysis to evaluate the effects of MSC therapy on DKD.…”