Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China; Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, China.
Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
Biochem Biophys Res Commun. 2022 Aug 27;618:127-132. doi: 10.1016/j.bbrc.2022.06.026. Epub 2022 Jun 11.
Nonalcoholic fatty liver disease (NAFLD) has been previously shown to be associated with diabetes mellitus (DM) which is one of the most decisive risk factors for the faster progression of NAFLD to nonalcoholic steatohepatitis (NASH), fibrosis or advanced cirrhosis. However, the critical molecular pathway involved in the development of diabetic-induced liver injury is unclear. By the proteomic study of liver from high-fat diet (HFD)/streptozotocin(STZ)-induced diabetic mice, we revealed that the upregulation of S100A9 was involved in the development of NAFLD with DM. Moreover, we found that S100A9 silencing decreased proinflammatory response and inhibited the TLR4-NF-κB signaling in in-vitro study. Our findings provide new perspectives into the pivotal role of S100A9 for development of diabetic NAFLD and revealed that S100A9 is a critical molecule that links liver injury to inflammation of NAFLD with DM.
非酒精性脂肪性肝病 (NAFLD) 先前已被证明与糖尿病 (DM) 相关，DM 是导致 NAFLD 向非酒精性脂肪性肝炎 (NASH)、纤维化或进展性肝硬化更快进展的最重要的决定因素之一。然而，糖尿病引起的肝损伤发展中涉及的关键分子途径尚不清楚。通过对高脂肪饮食 (HFD)/链脲佐菌素 (STZ) 诱导的糖尿病小鼠肝脏的蛋白质组学研究，我们发现 S100A9 的上调与伴有 DM 的 NAFLD 的发展有关。此外，我们发现 S100A9 沉默可减少促炎反应并抑制体外研究中的 TLR4-NF-κB 信号通路。我们的研究结果为 S100A9 在糖尿病性 NAFLD 发展中的关键作用提供了新的视角，并表明 S100A9 是将肝损伤与伴有 DM 的 NAFLD 的炎症联系起来的关键分子。
