神经/血管导向因子Netrin-1在胰岛中的抗炎功效及其在糖尿病治疗中的作用

Diabetes is one of the largest global health emergencies of the 21st century. Diabetes and its complications are major causes of death in most countries. It has been established that chronic inflammation plays a significant part in the pathogenesis of diabetes, which is a major risk factor of multiple diseases including cardiovascular disorders, atherosclerosis, diabetic nephropathy and cancer. Since diabetes and its co-morbidities are associated with over-active inflammation, an ideal treatment for diabetic individuals should not only address hyperglycaemia, but also aim to normalise pathologically elevated inflammatory tone. Netrin-1 is a multifunctional diffusible protein that plays an active role in regulating angiogenesis, cell migration and inflammation. After initial research that focused on its functions in axon patterning, Netrin-1 has later been implicated in the development of mammary gland and pancreas. Recent studies proposed a protective role of Netrin-1 against vascular inflammation, atherosclerosis, peritonitis, pancreatitis, acute kidney injury, pulmonary damage and ischeamia-induced hypoxia. Positive impact of Netrin-1 application was also implicated in diabetic nephropathy, diabetic retinopathy and diabetes-associated myocardial infarction. Given the beneficial effect of Netrin-1 in diabetes-associated disorders and its regenerative and anti-inflammatory properties, we are investigating the anti-inflammatory role of Netrin-1 in islets of Langerhans and its therapeutic potential against diabetes and diabetes-related disorders.

糖尿病是21世纪全球最大的公共卫生事件之一，我国的糖尿病患者总数超过1亿。慢性炎症性造成的机体免疫应答失衡是造成糖尿病的首要原因之一，也是引发糖尿病并发症的主要因素。Netrin-1是一神经/血管导向因子，其不仅在机体发育过程中对神经轴突的导向以及心血管生成具有引导作用，也可通过改善受损组织中炎症反应过激的微环境缓解组织损伤，具有潜在的抗炎功效。因此鉴于Netrin-1在抗炎及组织修复方面的潜在作用，本项目将使用小鼠模型及临床样本进行多层次分析，从细胞免疫学，特别是免疫应答及炎症角度围绕Netrin-1介导的免疫效应在胰岛功能、胰岛内免疫细胞行为、糖尿病引发的胰岛内免疫细胞浸润等方面的影响进行系统性的分析和评估。并综合评价抑炎因子治疗糖尿病及其并发症的可靠性，为治疗糖尿病及并发症寻找共同药物靶点。

糖尿病是21世纪全球最大的公共卫生事件之一，我国的糖尿病患者总数超过1亿。慢性炎症性造成的机体免疫应答失衡是造成糖尿病的首要原因之一，也是引发糖尿病并发症的主要因素。Netrin-1是一神经/血管导向因子，其不仅在机体发育过程中对神经轴突的导向以及心血管生成具有引导作用，也可通过改善受损组织中炎症反应过激的微环境缓解组织损伤，具有潜在的抗炎功效。因此鉴于Netrin-1在抗炎及组织修复方面的潜在作用，本项目将使用小鼠模型及临床样本进行多层次分析，从细胞免疫学，特别是免疫应答及炎症角度围绕Netrin-1介导的免疫效应在胰岛功能、胰岛内免疫细胞行为、糖尿病引发的胰岛内免疫细胞浸润等方面的影响进行系统性的分析和评估。并综合评价抑炎因子治疗糖尿病及其并发症的可靠性，为治疗糖尿病及并发症寻找共同药物靶点。通过该项目所支持的相关研究，我们发现通过免疫手段防控1型糖尿病的潜在可行性，并同时通过使用脂肪特异性敲处2型糖尿病小鼠模型，找到可影响2型糖尿病患者的成脂分化过程的Netrin-1相关的调控机制，有望在今后深入挖掘的基础上进一步探索并明确糖尿病相关疾病代谢的机制及重要靶点。