IL-37通过活化AMPK信号通路抑制糖尿病肾病肾间质纤维化的作用与机制研究

Renal fibrosis is the significant pathologic change in diabetic kidney disease (DKD) and inflammation acts as a major cause of this pathological phenomenon. Our previous studies suggested IL-37, an anti-inflammatory cytokine, has the ability to inhibit renal fibrosis in DKD, but the specific mechanism was still unclear. AMPK plays an important role in diabetes and its complications. Our work has revealed that AMPK inactivation is a major cause of renal fibrosis in DKD, and inflammation is involved in the progression. Based on recent findings that AMPK can be activated by IL-37, we then hypothesized that IL-37 may prevent renal fibrosis in DKD through stimulating AMPK activity. Therefore, in this study, we plan to carry out a study on IL-37tg mice and HK-2 cells to investigate the role of IL-37 activation of AMPK signaling pathway in inhibiting inflammation and epithelial-mesenchymal transition in renal tubular cells, and further discuss what is the mechanisms of IL-37 on mediating AMPK activity; Finally, to explore whether up-regulation of IL-37 could prevent renal fibrosis in DKD by mediating AMPK activity. This study aims to explore the therapeutic target in delaying the progression of DKD and elucidate its underlying mechanisms.

肾间质纤维化是糖尿病肾病（DKD）重要的病理改变，而炎症是其发生的关键诱因。我们前期研究发现，白细胞介素-37（IL-37）作为一种抑炎因子，可延缓DKD肾间质纤维化的发生，但其机制亟待阐明。AMPK在糖尿病及其并发症中扮演着非常关键的角色，我们的研究表明AMPK活性下降是DKD肾间质纤维化发生的重要诱因，机制与其参与炎症调节有关。而新近研究提示IL-37可激活AMPK信号活性。我们推测IL-37或许正是通过活化AMPK抑制了高糖诱导的炎症和DKD肾间质纤维化。为此，本项目拟以IL-37转基因小鼠和HK-2细胞为研究对象，明确IL-37通过活化AMPK抑制高糖诱导炎症及肾小管上皮细胞转分化的作用，并阐明IL-37活化AMPK的深层机制，评价IL-37过表达是否可以通过调控AMPK信号通路改善DKD肾间质纤维化。本研究旨在为DKD肾间质纤维化探索有效的防治措施，并深入揭示其内在机制。

肾间质纤维化是糖尿病肾病（DKD）重要的病理改变，而炎症是其发生的关键诱因。我们前期研究发现，白细胞介素-37（IL-37）作为一种抑炎因子，可延缓DKD肾间质纤维化的发生，但其机制亟待阐明。AMPK在糖尿病及其并发症中扮演着非常关键的角色，我们的研究表明AMPK活性下降是DKD肾间质纤维化发生的重要诱因，机制与其参与炎症调节有关。而新近研究提示IL-37可激活AMPK信号活性。我们推测IL-37或许正是通过活化AMPK抑制了高糖诱导的炎症和DKD肾间质纤维化。为此，本项目拟以IL-37转基因小鼠和HK-2细胞为研究对象，明确IL-37通过活化AMPK抑制高糖诱导炎症及肾小管上皮细胞转分化的作用，并阐明IL-37活化AMPK的深层机制，评价IL-37过表达是否可以通过调控AMPK信号通路改善DKD肾间质纤维化。本研究旨在为DKD肾间质纤维化探索有效的防治措施，并深入揭示其内在机制。