Data Sheet 2_Genetic and environmental factors associated with alteration of filtration slit proteins and their functions: a scoping review.xlsx

BackgroundFiltration slit proteins are important for maintaining the integrity of the glomerular filtration barrier. Genetic mutations and environmental factors can disrupt their structure and functions, leading to proteinuria and kidney diseases. This scoping review aims to synthesize the available information on the genetic and environmental factors that affect the slit proteins to enhance our understanding of the (patho)physiology of glomerular filtration.
MethodsOnline databases such as Wiley and PubMed were used. Relevant studies were selected focusing on genetic variations, environmental influences, and their impact on filtration slit proteins. Data extraction and synthesis were conducted to highlight key themes and knowledge gaps.
ResultsWe summarized at least 20 proteins and their genes, including nephrin, podocin, phospholipase C Epsilon 1 (PLCE1), CD2-Associated Protein (CD2AP), ITGA 3, synaptopodin, myosin 1E (MYO1E), flotillin-2 (Flot2), podocalyxin, FAT1, Apo Hemoglobin-Haptoglobin (Apo Hb-Hp), spermidine, P-Cadherin, ephrin B1, Zo- 1 (Zona Occluden), MAGI 1&2 (MAGUK inverted), Par- complex, IP-10 (interferon-inducible protein), neurexin 1, and liver type fatty acid binding protein. We also reported at least 8 environmental factors, including oxidative stress, inflammation, heavy metals, air-bone pollutants, high-fat diets, vitamins and micronutrient deficiency, mechanical stretch, and nephrotoxic agents.
ConclusionThis review highlights various filtration slit proteins and the mechanisms of their alterations by genetic and environmental factors. It contributes to efforts toward personalized therapeutic strategies for disorders of glomerular filtration.

背景：滤过裂隙蛋白（filtration slit proteins）对维持肾小球滤过屏障（glomerular filtration barrier）的完整性至关重要。遗传突变与环境因素可破坏其结构与功能，进而引发蛋白尿（proteinuria）与肾脏疾病。本次范围综述（scoping review）旨在梳理现有关于影响滤过裂隙蛋白的遗传与环境因素的相关研究，以加深我们对肾小球滤过病理生理学（pathophysiology）的认识。
方法：本研究检索了Wiley、PubMed等在线数据库，筛选聚焦于遗传变异、环境影响及其对滤过裂隙蛋白作用的相关研究。通过数据提取与综合分析，提炼核心研究主题与知识空白。
结果：本综述共汇总了至少20种蛋白及其编码基因，包括肾病蛋白（nephrin）、podocin（podocin）、磷脂酶Cε1（phospholipase C Epsilon 1, PLCE1）、CD2相关蛋白（CD2-Associated Protein, CD2AP）、整合素α3（ITGA 3）、突触足蛋白（synaptopodin）、肌球蛋白1E（myosin 1E, MYO1E）、flotillin-2（Flot2）、足涎蛋白（podocalyxin）、FAT1（FAT1）、载脂蛋白-血红蛋白-结合珠蛋白复合物（Apo Hemoglobin-Haptoglobin, Apo Hb-Hp）、亚精胺（spermidine）、P-钙黏蛋白（P-Cadherin）、ephrin B1（ephrin B1）、紧密连接蛋白Zo-1（Zo-1, Zona Occluden）、MAGI 1&2（MAGUK inverted, MAGI 1&2）、Par复合体（Par- complex）、干扰素诱导蛋白10（IP-10, interferon-inducible protein）、神经连接蛋白1（neurexin 1）以及肝脏型脂肪酸结合蛋白（liver type fatty acid binding protein）。此外，本综述还梳理了至少8种环境因素，包括氧化应激（oxidative stress）、炎症（inflammation）、重金属（heavy metals）、空气传播污染物（air-bone pollutants）、高脂饮食（high-fat diets）、维生素与微量营养素缺乏（vitamins and micronutrient deficiency）、机械牵拉（mechanical stretch）以及肾毒性物质（nephrotoxic agents）。
结论：本次范围综述明确了多种滤过裂隙蛋白及其因遗传与环境因素发生改变的分子机制，可为肾小球滤过相关疾病的个性化治疗策略提供研究支撑。