Researchers from the Third Xiangya Hospital of Central South University, Changsha, China found overexpressing c-Jun promoted accelerated wound healing.
The high levels of blood glucose common in people and animals with diabetes can lead to peripheral vascular disease, peripheral neuropathy, and an impaired immune response. The resultant decreased blood flow and lower immune cell migration to a wound impede the normal healing process. Medical approaches to consistently or reliably improve slow or nonhealing wounds is lacking. However, the use of mesenchymal stem cells (MSCs) is being studied as an intervention to promote better cutaneous wound healing. MSCs are crucial for regenerative wound healing because they have the capacity to enhance cellular differentiation, immune-modulation, and release of growth factors needed for angiogenesis and re-epithelialization, thus promoting healthy granulation tissue formation.On the molecular front, c-Jun and c-Fos make up the activator protein-1 (AP-1), a transcription factor involved in many biological processes. Studies have shown that c-Jun is crucial for the formation of the epidermal leading edge of wounds. To determine the role of c-Jun expression of MSCs in wound healing, a group of researchers from the Third Xiangya Hospital of Central South University, Changsha, China conducted studies with MSCs that under- or overexpress c-Jun in vitro and in vivo.
Silencing or overexpression of c-Jun was achieved via human umbilical cord-derived MSCs transfected with lentiviruses carrying either the full-length human c-Jun or an RNA targeting human c-Jun. Diabetes mellitus was induced with streptozocin administration in laboratory rats fed a diet high in glucose and fat. Wounds were created on the rats' dorsal skin, and the effects on wound closure of c-Jun silencing or overexpression in transfected MSCs were determined.
In vitro, the c-Jun−silenced MSCs showed decreased cell proliferation and migration, but MSCs overexpressing c-Jun exhibited increased proliferation. Rats that were injected subcutaneously with MSCs overexpressing c-Jun exhibited accelerated wound closure and enhanced revascularization and re-epithelialization at the wound bed. The results of the study show that c-Jun overexpression promotes MSC proliferation in vitro and enhanced wound closure in diabetic rats. Therefore, MSCs overexpressing c-Jun may be a clinical intervention that could provide a means to successfully address wound healing in patients with diabetes.
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Yue, C., Guo, Z., Luo, Y., Yuan, J., Wan, X., & Mo, Z. (2020). c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells. Stem Cells International, 2020, 1-10. doi: 10.1155/2020/7430968