既往研究发现肾小球固有细胞之间cross-talk在肾小球生理和病理中起重要作用，但目前仅有几个cross-talk被阐明。近年我们j对肾小球进行了单细胞RNA-seq，鉴定了一批系膜和足细胞必需基因。基于这些必需基因，我们设计了系膜细胞和足细胞之间cross-talk的新策略，并预测了若干新cross-talk模式。本研究将验证其中系膜细胞ANGPT2作用于足细胞ITGAV这一cross-talk在足细胞中的作用，研究内容包括：1）测试小鼠足细胞ITAGV敲除和系膜细胞ANGPT2敲低对足细胞的影响；2）明确糖肾中ANGPT2的上调是否参与糖肾足细胞损伤以及是否通过激活FAK信号；3）测试临床试验中的ANGPT2和ITGAV抑制药物能否治疗糖肾足细胞损伤。本研究不仅能加深足细胞生理病理机制的理解并为糖肾提供新疗法，还将证明我们cross-talk鉴定新方法的可行性，为其他研究者所用。

Previous studies have shown that cross-talks between different glomerular cell types are essential for glomerular structure and function. However, due to lack of efficient experimental methods, there are only several glomerular cross-talks that have been identified so far. In recent years, we performed single-cell RNA-seq on glomerular cells and identified a batch of genes essential for podocytes and mesangial cells. Based on these genes, we designed an novel approach to identify cross-talks between mesangial cells and podocytes and predicted several new candidate cross-talks, including mesangial cells-secreted ANGPT2 that may act on ITGAV receptor on podocytes. To validate this new cross-talk between mesangial cells and podocytes via ANGPT2-ITGAV, we will test its role in podocyte physiology and pathology by determining 1) whether mouse podocyte-specific ITGAV knockout and mesangial cells-specific ANGPT2 knockdown would cause podocyte injury; 2) whether upregulation of ANGPT2 as observed in the glomeruli of both diabetic mice and patients (i.e.,strengthened cross-talk) is involved in podocyte injury in DN and whether it is through FAK pathway; 3) whether the inhibitor drugs of ANGPT2 and ITGAV that are clinically approved or on clinical trials would alleviate diabetes-induced podocyte injury.These studies would provide new insights into podocyte physiology and pathology and potentially provide new treatments for DN; in addition, it would also demonstrate the feasibility of the approach we have designed to identify novel cross-talk between different types of cells, providing a new tool for researchers in the field.