Exosomes from hypoxic pretreated BMSCs attenuate primary Sjögren's syndrome-induced skin injury via PPARγ-mediated M2-like macrophage activation

Background

Sjögren's syndrome (SS) is an autoimmune disorder identified by a triad of sicca symptoms, pain, and fatigue. SS-induced skin injury seriously affects people's health but remains unsolved. Accumulating investigations have confirmed that exosomes (Exos) originating from bone marrow mesenchymal stem cells (BMSCs) can bolster the stressed microenvironment and tissue repair. Present study aimed to unravel therapeutic effects regarding BMSC Exos on SS-induced skin injury.

Methods

In this study, an SS mouse model was constructed, and exosomes from BMSCs (Exos) and hypoxic pretreated BMSCs (HExos) were isolated. The therapeutic effects of exosomes in SS were identified using ELISA, immunohistochemistry, and immunofluorescence. High-throughput sequencing (HTS) was utilized to characterize differentially expressed genes between Exos and HExos.

Results

The data showed that Exos, especially HExo treatments, affected the inhibition of SS-induced inflammatory factor expression, cell apoptosis, ROS deposition, and collagen loss. HTS and RT-qPCR detection showed PPARγ functioned importantly for HExo-mediated protective effects against SS-induced skin injury. The in vitro experiment using RAW confirmed that PPARγ expression inhibited LPS-induced M1-like macrophage activation, which was confirmed using the PPARγ antagonist T0070907. PPARγ upregulation improved therapeutic effects regarding Exos upon skin injury in SS mice by promoting M2-like macrophage activation.

Conclusion

Taken together, our study found that exosomes from hypoxic pretreated BMSCs attenuated primary Sjögren's syndrome-induced skin injury via PPARγ delivery and promoted M2-like macrophage activation.