Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People' s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518020, China; Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Aug 1;1243:124231. doi: 10.1016/j.jchromb.2024.124231. Epub 2024 Jul 5.
Diabetic nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN. 5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Significantly, the expression of multiple heat shock proteins (HSPs), tubulins, and heterogeneous nuclear ribonucleoproteins (hnRNPs) in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the protein-protein interaction (PPI) analysis of DEPs in both glomeruli and renal tubules. In this study, we delve into the unique proteomic characteristics of each sub-region of renal tissue. This enhances our understanding of the potential pathophysiological changes in DN, particularly the potential involvement of glycolysis metabolic disorder, glomerular cytoskeleton and cell junctions. These insights are crucial for further research into the identification of disease biomarkers and the pathogenesis of DN.
糖尿病肾病（DN）仍然是终末期肾病（ESRD）的主要原因，在其诊断和干预中需要同等关注和单独分析肾小球、肾小管和肾间质病变。本研究旨在确定 DN 的特定蛋白质组学特征，并评估与 DN 相关的生物学过程的变化。选择 5 例 DN 患者和 5 例健康肾移植供体对照进行分析。通过激光捕获显微镜（LCM）获得肾小球、肾小管和肾间质组织的蛋白质组学特征，使用高效液相色谱-串联质谱（HPLC-MS/MS）进行研究。重要的是，肾小球和肾小管中的多种热休克蛋白（HSPs）、微管蛋白和异质核核糖核蛋白（hnRNPs）的表达明显降低。肾小球和肾小管中的差异表达蛋白（DEPs）在与细胞连接和细胞运动相关的途径中表现出明显的富集，包括肌动蛋白细胞骨架和紧密连接的调节。肾小管中的 DEPs 在葡萄糖代谢相关途径中显著富集，如葡萄糖代谢、糖酵解/糖异生和柠檬酸循环。此外，糖酵解/糖异生途径是 DN 肾小球和肾小管中共同富集的途径。值得注意的是，在肾小球和肾小管的 DEPs 的蛋白质-蛋白质相互作用（PPI）分析中，ACTB 是最重要的蛋白质。在本研究中，我们深入研究了肾组织每个亚区的独特蛋白质组学特征。这增强了我们对 DN 潜在病理生理变化的理解，特别是糖代谢紊乱、肾小球细胞骨架和细胞连接的潜在参与。这些见解对于进一步研究疾病生物标志物的识别和 DN 的发病机制至关重要。
