RNA sequencing of wild Type, Rictor-KO or GATA3-KO J774.1 cells

Purpose: Endosomal-lysosomal system is one of the pivotal degradation system for a varieties of extracellular substances, of which dysfunction has been indicated to be associated with cardiovascular and neurodegenerative diseases. This degradation process consists of multiple steps; uptake of extracellular molecules, endosomal formation and its transportation to lysosomes, and digestion by lysosomal enzymes. Whereas TFEB, is a transcriptional factor, has been well studied as a master regulator of cellular uptake and lysosomal function, a key regulatory mechanism for endosomal maturation remains unclear. We previously found that isorhamnetin, a dietary flavonoid, enhanced the endosomal-lysosomal proteolysis in J774.1 macrophage-like cell line, which was independent on mTORC1-TFEB axis. In this study, we analyzed the molecular mechanism of activated endosomal-lysosomal degradation by isorhamnetin. mRNA profiles of wild type, rictor-KO or GATA3-KO J774.1 treated with isorhamnetin

研究目的：内体-溶酶体系统是多种胞外物质的关键降解系统之一，其功能异常已被证实与心血管疾病及神经退行性疾病密切相关。该降解过程涵盖多个步骤：胞外分子的摄取、内体的形成及其向溶酶体的转运，以及溶酶体酶介导的消化过程。尽管转录因子EB（TFEB）作为细胞摄取与溶酶体功能的核心调控因子已被广泛研究，但内体成熟的关键调控机制仍不明确。本团队前期研究发现，膳食黄酮类化合物异鼠李素（isorhamnetin）可在J774.1巨噬细胞样细胞系中增强内体-溶酶体蛋白水解过程，且该过程不依赖于mTORC1-TFEB信号轴。本研究旨在解析异鼠李素激活内体-溶酶体降解通路的分子机制，我们对经异鼠李素处理的野生型、rictor-KO及GATA3-KO J774.1细胞的mRNA表达谱进行了分析。