Mesenchymal stromal cells ameliorate acute lung injury induced by LPS mainly through stanniocalcin-2 mediating macrophage polarization

作者：Haijin Lv, Qiuli Liu, Yao Sun, Xiaomeng Yi, Xuxia Wei, Wei Liu, Qi Zhang, Huimin Yi, Guihua Chen · 发表于：Annals of Translational Medicine · 年份：2020 · DOI：10.21037/atm.2020.02.105 · 被引用次数：47 · 研究领域：Mesenchymal stem cell research、Physiological and biochemical adaptations、Neonatal Respiratory Health Research

Background: Acute lung injury (ALI) is a devastating syndrome with no effective pharmacological therapies in the clinic. Mesenchymal stromal cells (MSCs) have been demonstrated to promote inflammation resolution and tissue repair in ALI. However, the specific mechanisms of this have not been clearly elucidated. Stanniocalcin-2 (STC2) is a stress-responsive protein that has anti-oxidative properties. Our previous study found that STC2 is a highly expressed stanniocalcin in MSCs, which may be involved in immunomodulatory activities. However, the role of STC2 in MSCs to resolve ALI has never been elucidated. Methods: Specific shRNA was used to downregulate STC2 in MSCs. We detected ROS, cell apoptosis, and paracrine factors changes in MSCs. STC2-associated antioxidant genes were also investigated by Co-immunoprecipitation (Co-IP) and immunofluorescence. Macrophage (THP1 cells) phenotype transitions were measured by flow cytometry after coculturing with MSCs in vitro. Then, we used MSCs to treat LPS-induced ALI in mice, and assessed injury scores inflammation, and antioxidant activities in the lungs of the mice. Alveolar macrophage (AM) phenotypes and CFSE-labeled MSC apoptosis in collected bronchoalveolar fluids (BALF) were also analyzed by flow cytometry. Results: After the STC2 knockdown, MSCs increased ROS generation and cell apoptosis after PX12 pretreatment. The antioxidant protein Nrf2 was colocalized with STC2 in the nucleus. A lack of STC2 expression in MSCs produced les...