Piezo1 Knockdown Activates PI3K/AKT and Enhances SPP1 to Drive M2 Macrophage Polarization and Reduce Cardiac Inflammation

We have successfully established a mouse model with myeloid cell-specific knockdown of Piezo1. The intraperitoneal injection of lipopolysaccharide (LPS) resulted in a significant increase in cardiac macrophage infiltration, as well as an increase in the expression of inflammatory factors and the inflammatory response. However, myeloid cell-specific knockdown of Piezo1 impaired this response, leading to an increase in macrophage polarization towards the M2 type and the decreased inflammatory response. As a result, myocardial injury caused by sepsis was attenuated. We have also demonstrated that the PI3K/AKT pathway is significantly activated after Piezo1 knockdown, resulting in reduced myocardial dysfunction. Overall design: RNA-sequencing profiling of macrophages from Piezo1^flox/flox and Piezo1^flox/flox Lyz2-Cre C57BL/6J mice following lipopolysaccharide (LPS) treatment.

本研究成功构建了髓系细胞特异性敲低Piezo1（Piezo1）的小鼠模型。腹腔注射脂多糖（lipopolysaccharide，LPS）可显著诱导心脏巨噬细胞浸润增加，同时上调炎症因子表达并增强炎症应答。然而，髓系细胞特异性敲低Piezo1可削弱该炎症应答，促使巨噬细胞向M2型极化，并降低炎症反应程度，最终减轻脓毒症引发的心肌损伤。本研究同时证实，Piezo1敲低后PI3K/AKT通路（PI3K/AKT pathway）显著激活，进而改善心肌功能障碍。实验整体设计：对经脂多糖（LPS）处理的Piezo1^flox/flox小鼠及Piezo1^flox/flox 溶菌酶2-Cre（Lyz2-Cre）C57BL/6J小鼠的巨噬细胞开展RNA测序（RNA-sequencing）分析。