慢性炎症是急性肾损伤慢性化（AKI-CKD）的关键环节，厘清AKI后炎症反应持续存在的机制是目前亟待解决的科学问题。我们发现，在AKI肾脏微环境作用下骨髓来源的CCR2– Ly6C intermediate(int)单核细胞在肾脏持续向CCR2–Ly6C–巨噬细胞(Mø)分化，后者分泌多种细胞因子加重肾脏损伤、激活淋巴细胞和肌成纤维细胞，导致炎症迁延不愈。据此，我们推测抑制Ly6Cint CCR2–单核细胞向Ly6C–CCR2–Mø分化，既能保留Ly6Cint Mø的修复功能、又抑制Ly6C–CCR2–Mø的致CKD作用，最终将延缓AKI慢性化。本研究拟利用多种生物示踪技术进一步证实该分化的合理性，并通过高通量测序、染色质免疫沉淀等方法寻找调节该分化的转录因子及Ly6C–CCR2–Mø的特异膜蛋白，设计生物靶向药物，明确单核细胞分化对AKI慢性化的影响和机制，为逆转AKI-CKD提供新手段

Patients who survive acute kidney injury (AKI) have a greater risk for chronic kidney disease (CKD), and recent clinical studies have shown that even a single episode of AKI can lead to subsequent CKD, however, the mechanisms for this “AKI to CKD progression” are still unknown. The chronic inflammation is increasingly recognized as an important determinant factor for this progression, but how to resolve the aberrant inflammation after AKI is full of challenges. Our recent studies have demonstrated that under renal microenvironment, bone marrow-derived Ly6C intermediate(int)CCR2– monocytes accumulate into kidney and differentiate into Ly6C–CCR2– Mø, which aggravates tubular damage, activates lymphocytes and myofibroblasts by secreting various cytokines, and accelerates chronic inflammation and progressive fibrosis. As the Ly6Cint macrophages in the injured kidney have a wound healing phenotype, we supposed that inhibition of the transdifferentiation of Ly6CintCCR2– monocytes into CCR2-Ly6C– Mø will break the balance between pro- and anti-inflammatory responses via polarizing Ly6CintCCR2– monocytes into anti-inflammatory Ly6Cint Mø, which offset the aberrant inflammation induced by CCR2-Ly6C– Mø and support tubular regeneration. In this study, we will use biological tracer techniques to confirm the transdifferentiation of Ly6CintCCR2– monocytes into CCR2-Ly6C– Mø in the AKI to CKD progression, and use high-throughput sequencing methods to identify the transcription factors in the regulation of transdifferentiation and the specific membrane protein of Ly6C–CCR2– Mø, and design targeted biologic drugs to explore wheather targeting on membrane protein or transcription factors related to transdifferentiation into Ly6C–CCR2– Mø can stop the AKI to CKD progression.