miR-200a-3p in Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Attenuates UVB-Induced Skin Inflammatory Response and Oxidative Stress via Keap1-Nrf2 Pathway

TL;DR

Exosomes from umbilical cord stem cells reduce UVB-induced skin damage by lowering inflammation and oxidative stress through the Keap1-Nrf2 pathway.

Contribution

miR-200a-3p in HuMSC-Exos is identified as a novel mediator of UVB skin protection via Keap1 inhibition.

Findings

HuMSC-Exos reduced ROS levels and proinflammatory cytokines in UVB-exposed cells and mice.

miR-200a-3p in HuMSC-Exos targets Keap1 to activate Nrf2 and upregulate antioxidant genes.

In vivo, HuMSC-Exos attenuated UVB-induced skin injury by modulating Nrf2 signaling.

Abstract

Ultraviolet (UV) radiation induces skin damage primarily through oxidative stress and excessive inflammation. Exosomes derived from mesenchymal stem cells have emerged as promising therapeutic agents for tissue repair. Here, we investigated the protective effects of human umbilical cord mesenchymal stem cell-derived exosomes (HuMSC-Exos) on UVB-induced skin injury in HaCaTs and C57BL/6 mice. HuMSC-Exos significantly reduced reactive oxygen species (ROS) levels, suppressed proinflammatory cytokines (IL-1β, TNF-α, and IL-6), and improved cell migration. Mechanistically, HuMSC-Exos inhibited Keap1, enhanced both total and phosphorylated Nrf2 expression, promoted its nuclear translocation, and upregulated antioxidant genes (HMOX1, NQO1, CAT, and SOD2). miR-200a-3p in HuMSC-Exos mediated these effects by targeting Keap1. Furthermore, preliminary data suggested that HuMSC-Exos also attenuate inflammatory responses via the NF-κB pathway. In vivo, HuMSC-Exos attenuated UVB-induced skin injury and inflammation by activating the Nrf2 signaling cascade. Collectively, our findings reveal a novel protective mechanism and highlight the therapeutic potential of HuMSC-Exos in mitigating UV-induced skin damage by modulating oxidative stress and inflammation.

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